Clinvar annotation not appearing

[robert-a-forsyth]

I was having issues with no Clinvar variants being annotated in my tumor vcf file, so I have tried a test with a single variant which is in the Clinvar vcf I have.

here is my test vcf file

##fileformat=VCFv4.2
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
chr13	32316461	.	A	G	60	PASS	.

here is the variant in my clinvar vcf

chr13	32316461	216026	A	G	.	.	ALLELEID=213018;CLNDISDB=MONDO:MONDO:0003582,MeSH:D061325,MedGen:C0677776,Orphanet:145;CLNDN=Hereditary_breast_ovarian_cancer_syndrome;CLNHGVS=NC_000013.11:g.32316461A>G;CLNREVSTAT=criteria_provided,_single_submitter;CLNSIG=Pathogenic;CLNSIGSCV=SCV000253750;CLNVC=single_nucleotide_variant;CLNVCSO=SO:0001483;CLNVI=ClinGen:CA335967;GENEINFO=BRCA2:675;MC=SO:0001582|initiator_codon_variant,SO:0001583|missense_variant;ORIGIN=1;RS=863224464

here is my script

vep -i test.vcf.gz \
 --format vcf \
 --dir . \
 --fasta Homo_sapiens_assembly38.fasta \
 -o vep_test.vcf \
 --vcf \
 --offline \
 --cache \
 --everything \
 --check_existing \
 --custom clinvar.chr.vcf.gz,ClinVar,vcf,exact,1,CLNSIG,CLNREVSTAT \
 --dir_cache VEP/cache

here is my output, which doesn't seem to have the expected CLNSIG column filled with pathogenic

##fileformat=VCFv4.2
##VEP="v111" time="2025-06-04 16:34:04" cache="VEP/cache/homo_sapiens/111_GRCh38" ensembl-variation=111.d616b1e ensembl-funcgen=111.5327cdd ensembl=111.a6cc543 ensembl-io=111.dbba8d6 1000genomes="phase3" COSMIC="98" ClinVar="202306" HGMD-PUBLIC="20204" assembly="GRCh38.p14" dbSNP="156" gencode="GENCODE 45" genebuild="2014-07" gnomADe="r2.1.1" gnomADg="v3.1.2" polyphen="2.2.3" regbuild="1.0" sift="6.2.1"
##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc|HGVSp|cDNA_position|CDS_position|Protein_position|Amino_acids|Codons|Existing_variation|DISTANCE|STRAND|FLAGS|VARIANT_CLASS|SYMBOL_SOURCE|HGNC_ID|CANONICAL|MANE_SELECT|MANE_PLUS_CLINICAL|TSL|APPRIS|CCDS|ENSP|SWISSPROT|TREMBL|UNIPARC|UNIPROT_ISOFORM|SOURCE|GENE_PHENO|SIFT|PolyPhen|DOMAINS|miRNA|HGVS_OFFSET|AF|AFR_AF|AMR_AF|EAS_AF|EUR_AF|SAS_AF|gnomADe_AF|gnomADe_AFR_AF|gnomADe_AMR_AF|gnomADe_ASJ_AF|gnomADe_EAS_AF|gnomADe_FIN_AF|gnomADe_NFE_AF|gnomADe_OTH_AF|gnomADe_SAS_AF|gnomADg_AF|gnomADg_AFR_AF|gnomADg_AMI_AF|gnomADg_AMR_AF|gnomADg_ASJ_AF|gnomADg_EAS_AF|gnomADg_FIN_AF|gnomADg_MID_AF|gnomADg_NFE_AF|gnomADg_OTH_AF|gnomADg_SAS_AF|MAX_AF|MAX_AF_POPS|CLIN_SIG|SOMATIC|PHENO|PUBMED|MOTIF_NAME|MOTIF_POS|HIGH_INF_POS|MOTIF_SCORE_CHANGE|TRANSCRIPTION_FACTORS|ClinVar|ClinVar_CLNSIG|ClinVar_CLNREVSTAT">
##INFO=<ID=ClinVar,Number=.,Type=String,Description="[PATH]/clinvar.chr.vcf.gz">
##INFO=<ID=ClinVar_CLNSIG,Number=.,Type=String,Description="CLNSIG field from [PATH]/clinvar.chr.vcf.gz">
##INFO=<ID=ClinVar_CLNREVSTAT,Number=.,Type=String,Description="CLNREVSTAT field from [PATH]/clinvar.chr.vcf.gz">
##VEP-command-line='vep --cache --check_existing --custom [PATH]/clinvar.chr.vcf.gz,ClinVar,vcf,exact,0,CLNSIG,CLNREVSTAT --database 0 --dir . --dir_cache [PATH]/cache --everything --fasta [PATH]/Homo_sapiens_assembly38.fasta --format vcf --input_file [PATH]/test.vcf.gz --offline --output_file vep_test.vcf --vcf'
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
chr13	32316461	.	C	T	.	PASS	CSQ=T|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000345108|protein_coding||||||||||COSV61525409|4507|-1||SNV|HGNC|HGNC:37116||||1|P1|CCDS45023.1|ENSP00000344616|A6NP61.105||UPI00006C1387||||||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000380152|protein_coding|2/27||ENST00000380152.8:c.1A>T|ENSP00000369497.3:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|YES|NM_000059.4||5|P2|CCDS9344.1|ENSP00000369497|P51587.237||UPI00001FCBCC|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000470094|nonsense_mediated_decay|2/28||ENST00000470094.2:c.1A>T|ENSP00000434898.2:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101||||5|||ENSP00000434898||H0YE37.46||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000528762|nonsense_mediated_decay|2/28||ENST00000528762.2:c.1A>T|ENSP00000433168.2:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101||||4|||ENSP00000433168||H0YD86.55||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|5_prime_UTR_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000530893|protein_coding|2/27||ENST00000530893.7:c.-365A>T||203|||||COSV61525409||1||SNV|HGNC|HGNC:1101||||1|A2||ENSP00000499438||A0A590UJI7.12||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000533490|protein_coding||||||||||COSV61525409|1098|-1||SNV|HGNC|HGNC:37116|YES|NM_001136571.2||5|P1|CCDS45023.1|ENSP00000437289|A6NP61.105||UPI00006C1387||||||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000544455|protein_coding|2/27||ENST00000544455.6:c.1A>T|ENSP00000439902.1:p.Leu1?|100|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101||||1|P2|CCDS9344.1|ENSP00000439902|P51587.237||UPI00001FCBCC|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|synonymous_variant&NMD_transcript_variant|LOW|BRCA2|ENSG00000139618|Transcript|ENST00000614259|nonsense_mediated_decay|1/26||ENST00000614259.2:c.1A>T|ENSP00000506251.1:p.Leu1%3D|1|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101||||2|||ENSP00000506251||A0A7P0TAP7.8|UPI00194D3080|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000665585|nonsense_mediated_decay|2/29||ENST00000665585.2:c.1A>T|ENSP00000499570.2:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|||||||ENSP00000499570||A0A590UJU6.13||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000666593|nonsense_mediated_decay|2/26||ENST00000666593.2:c.1A>T|ENSP00000499256.2:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|||||||ENSP00000499256||A0A590UJ24.11||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000680887|protein_coding|2/27||ENST00000680887.1:c.1A>T|ENSP00000505508.1:p.Leu1?|126|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|||||P2|CCDS9344.1|ENSP00000505508|P51587.237|A0A7P0T9D7.7|UPI00001FCBCC|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700199|retained_intron|2/2||ENST00000700199.1:n.125A>T||125|||||COSV61525409||1||SNV|HGNC|HGNC:1101|||||||||||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700200|retained_intron|2/6||ENST00000700200.1:n.125A>T||125|||||COSV61525409||1||SNV|HGNC|HGNC:1101|||||||||||||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700201|nonsense_mediated_decay|2/11||ENST00000700201.1:c.1A>T|ENSP00000514855.1:p.Leu1?|123|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|||||||ENSP00000514855||A0A8V8TQQ4.3|UPI0020AFDD7C|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700202|protein_coding|2/27||ENST00000700202.2:c.1A>T|ENSP00000514856.2:p.Leu1?|200|1|1|L|Ctg/Ttg|COSV61525409||1||SNV|HGNC|HGNC:1101|||||A2||ENSP00000514856||A0A8V8TPZ2.3|UPI00201AF897|||1|||||||||||||||||||||||||||||||||||1|1|||||||||,T|regulatory_region_variant|MODIFIER|||RegulatoryFeature|ENSR00000060894|promoter||||||||||COSV61525409||||SNV||||||||||||||||||||||||||||||||||||||||||||||||||1|1|||||||||

[dglemos]

Hi @robert-a-forsyth,
In your example the input variant is chr13 32316461 A/G, however in the output the alleles are C/T. Can you double check your input alleles?

For the following input variant:

##fileformat=VCFv4.2
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
chr13	32316461	.	A	G	60	PASS	.

This is the VEP output:

#CHROM  POS     ID      REF     ALT     QUAL    FILTER  INFO
chr13   32316461        .       A       G       .       .       CSQ=G|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000345108|protein_coding|||||||||||4507|-1||HGNC|HGNC:37116||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000380152|protein_coding|2/27||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000470094|nonsense_mediated_decay|2/28||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000528762|nonsense_mediated_decay|2/28||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|5_prime_UTR_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000530893|protein_coding|2/27||||203|||||||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000533490|protein_coding|||||||||||1098|-1||HGNC|HGNC:37116||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000544455|protein_coding|2/27||||100|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000614259|nonsense_mediated_decay|1/26||||1|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000665585|nonsense_mediated_decay|2/29||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000666593|nonsense_mediated_decay|2/26||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000680887|protein_coding|2/27||||126|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700199|retained_intron|2/2||||125|||||||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700200|retained_intron|2/6||||125|||||||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700201|nonsense_mediated_decay|2/11||||123|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter,G|start_lost|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700202|protein_coding|2/27||||200|1|1|M/V|Atg/Gtg|||1||HGNC|HGNC:1101||216026|Pathogenic|criteria_provided&_single_submitter

As you can see the variant is annotated as Pathogenic.

Here is the variant in the Clinvar VCF file from 2025-06-01:
13 32316461 216026 A G . . ALLELEID=213018;CLNDISDB=MONDO:MONDO:0003582,MeSH:D061325,MedGen:C0677776,Orphanet:145;CLNDN=Hereditary_breast_ovarian_cancer_syndrome;CLNHGVS=NC_000013.11:g.32316461A>G;CLNREVSTAT=criteria_provided,_single_submitter;CLNSIG=Pathogenic;CLNSIGSCV=SCV000253750;CLNVC=single_nucleotide_variant;CLNVCSO=SO:0001483;CLNVI=ClinGen:CA335967;GENEINFO=BRCA2:675;MC=SO:0001582|initiator_codon_variant,SO:0001583|missense_variant;ORIGIN=1;RS=863224464

[robert-a-forsyth]

I notice this as well, but the input is definitely

#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
chr13	32316461	.	A	G	60	PASS	.

if there is a setting or something in the script which is causing some flipping behavior I'm not aware of it. But that is definitely my output for this input and script

[dglemos]

The alleles should not be flipped.
Please download the following fasta file: https://ftp.ensembl.org/pub/current_fasta/homo_sapiens/dna/Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz

and try again with the following command:

vep -i test.vcf.gz \
 --format vcf \
 --dir . \
 --fasta Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz \
 -o vep_test.vcf \
 --vcf \
 --offline \
 --custom clinvar.chr.vcf.gz,ClinVar,vcf,exact,1,CLNSIG,CLNREVSTAT \
 --dir_cache VEP/cache

[robert-a-forsyth]

This is my output with that command and fasta file
I still observe the different REF and ALT values and no clinvar annotation

##fileformat=VCFv4.2
##VEP="v111" time="2025-06-05 12:57:29" cache="/staging/leuven/stg_00096/home/rforsyth/leukaemia/VEP/cache/homo_sapiens/111_GRCh38" ensembl-io=111.dbba8d6 ensembl-variation=111.d616b1e ensembl=111.a6cc543 ensembl-funcgen=111.5327cdd 1000genomes="phase3" COSMIC="98" ClinVar="202306" HGMD-PUBLIC="20204" assembly="GRCh38.p14" dbSNP="156" gencode="GENCODE 45" genebuild="2014-07" gnomADe="r2.1.1" gnomADg="v3.1.2" polyphen="2.2.3" regbuild="1.0" sift="6.2.1"
##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc|HGVSp|cDNA_position|CDS_position|Protein_position|Amino_acids|Codons|Existing_variation|DISTANCE|STRAND|FLAGS|SYMBOL_SOURCE|HGNC_ID|SOURCE|ClinVar|ClinVar_CLNSIG|ClinVar_CLNREVSTAT">
##INFO=<ID=ClinVar,Number=.,Type=String,Description="[PATH]/clinvar.chr.vcf.gz">
##INFO=<ID=ClinVar_CLNSIG,Number=.,Type=String,Description="CLNSIG field from [PATH]/clinvar.chr.vcf.gz">
##INFO=<ID=ClinVar_CLNREVSTAT,Number=.,Type=String,Description="CLNREVSTAT field from [PATH]/clinvar.chr.vcf.gz">
##VEP-command-line='vep --custom [PATH]/clinvar.chr.vcf.gz,ClinVar,vcf,exact,1,CLNSIG,CLNREVSTAT --database 0 --dir . --dir_cache [PATH]/cache --fasta Homo_sapiens.GRCh38.dna.primary_assembly.fa --format vcf --input_file test.vcf.gz --offline --output_file vep_test.vcf --vcf'
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
chr13	32316461	.	C	T	.	PASS	CSQ=T|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000345108|protein_coding|||||||||||4507|-1||HGNC|HGNC:37116||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000380152|protein_coding|2/27||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000470094|nonsense_mediated_decay|2/28||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000528762|nonsense_mediated_decay|2/28||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|5_prime_UTR_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000530893|protein_coding|2/27||||203|||||||1||HGNC|HGNC:1101||||,T|upstream_gene_variant|MODIFIER|ZAR1L|ENSG00000189167|Transcript|ENST00000533490|protein_coding|||||||||||1098|-1||HGNC|HGNC:37116||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000544455|protein_coding|2/27||||100|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|synonymous_variant&NMD_transcript_variant|LOW|BRCA2|ENSG00000139618|Transcript|ENST00000614259|nonsense_mediated_decay|1/26||||1|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000665585|nonsense_mediated_decay|2/29||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000666593|nonsense_mediated_decay|2/26||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000680887|protein_coding|2/27||||126|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700199|retained_intron|2/2||||125|||||||1||HGNC|HGNC:1101||||,T|non_coding_transcript_exon_variant|MODIFIER|BRCA2|ENSG00000139618|Transcript|ENST00000700200|retained_intron|2/6||||125|||||||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant&NMD_transcript_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700201|nonsense_mediated_decay|2/11||||123|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||,T|start_lost&synonymous_variant|HIGH|BRCA2|ENSG00000139618|Transcript|ENST00000700202|protein_coding|2/27||||200|1|1|L|Ctg/Ttg|||1||HGNC|HGNC:1101||||

[dglemos]

I'm unable to reproduce the issue.
Can you please send the input file so I can test it locally?

[robert-a-forsyth]

test.vcf.gz
And I used

curl -O https://ftp.ensembl.org/pub/release-114/variation/indexed_vep_cache/homo_sapiens_vep_111_GRCh38.tar.gz

and this clinvar vcf here

[dglemos]

Thanks!
The input file you send me has alleles C/T.