gnomad annotations question

[apaul7]

Hi!
I really appreciate you creating this tool. I have a question about the gnomad benign annotations in the latest version(v3.4.6) of annotsv. I've used the default annotations provided when installing annotsv.

My issue is with gnomad variant gnomAD-SV_v3_DEL_chr3_74d6df2b. This entry can be found in the $install/Annotations_Human/SVincludedInFt/BenignSV/GRCh38/benign_Loss_SV_GRCh38.sorted.bed file:

$ grep "DEL_chr3_74D6DF2B" benign_Loss_SV_GRCh38.sorted.bed
3       16955863        54461038        gnomAD-SV_v3_DEL_chr3_74d6df2b  chr3:16955863-54461038  0.1881

The same event can be found on the gnomad website. The issue is that the gnomad website has the does not have the variant filter status as PASS.

The readme says the benign calls are filtered for a few things:
• Allele frequency ≥ 1% (AF ≥ 0.01) (default, see the “-benignAF” option in USAGE/OPTIONS)
• At least 5 homozygous individuals (N_HOMALT ≥ 5)
• ≥ 500 individuals tested (AN ≥ 1000)
• “DUP”, “DEL”, “INS” or “INV” SV type
• FILTER = PASS

I downloaded the gnomad sv bed file and confirmed the event is not PASS

is this an issue with the benign annotations?
Thanks!
-Alex

[lgmgeo]

Hi Alex,

Thank you for your interest in AnnotSV.

I'm quite surprised because I do not have gnomAD-SV_v3_DEL_chr3_74d6df2b in my install:

Do you run AnnotSV with the annotations distributed with the V3.4.6?

Best,

Véronique

[apaul7]

interesting! I followed the install procedure in the make file. Let me redownload the annotations and see if I have the same problem.

[lgmgeo]

Disturbing...
Can another user verify this?

[lgmgeo]

Do you have the same file size?
(for benign_Loss_SV_GRCh38.sorted.bed)

[apaul7]

I still had the annotation tar file from my installation:

$ md5sum Annotations_Human_3.4.6.tar.gz
a0a4df58d3ed719121d935d1a28f363c  Annotations_Human_3.4.6.tar.gz

$ tar -zxvf Annotations_Human_3.4.6.tar.gz
...
...

$ grep "74d6df2b" Annotations_Human/SVincludedInFt/BenignSV/GRCh38/benign_Loss_SV_GRCh38.sorted.bed
3       16955863        54461038        gnomAD-SV_v3_DEL_chr3_74d6df2b  chr3:16955863-54461038  0.1881

$ md5sum Annotations_Human/SVincludedInFt/BenignSV/GRCh38/benign_Loss_SV_GRCh38.sorted.bed
a3fe6f31f468c08f1ef71620f63fd806  Annotations_Human/SVincludedInFt/BenignSV/GRCh38/benign_Loss_SV_GRCh38.sorted.bed

I am re downloading the annotation bundle from https://www.lbgi.fr/~geoffroy/Annotations/Annotations_Human_3.4.6.tar.gz to confirm that the md5sum I have downloaded matches.

[apaul7]

looks to be the same file:

$ curl -C - -LO https://www.lbgi.fr/~geoffroy/Annotations/Annotations_Human_3.4.6.tar.gz
  % Total    % Received % Xferd  Average Speed   Time    Time     Time  Current
                                 Dload  Upload   Total   Spent    Left  Speed
100 2025M  100 2025M    0     0  1539k      0  0:22:27  0:22:27 --:--:-- 2174k

$ md5sum Annotations_Human_3.4.6.tar.gz
a0a4df58d3ed719121d935d1a28f363c  Annotations_Human_3.4.6.tar.gz

[lgmgeo]

Thank you for reporting the bug.
I will do my best to provide a new annotation update as soon as possible.

[lgmgeo]

AnnotSV 3.5 is now available with annotation update.