VEP not returning gnomAD AF

Question

[michal.inbar]

Hi,

Any Idea why I'm not getting any gnomAD results for NM_001029.3:c.-22C>G?

Here it is in gnomAD: https://gnomad.broadinstitute.org/variant/12-56435929-C-G?dataset=gnomad_r2_1

my VEP results: http://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Results?tl=7ESUIe0HqyqjbgAq-6066193

thanks!

Emily_Ensembl

[manuel.belmadani]

You could try wAnnovar which seems to work for that variant.

Answer 1

[Ben_Ensembl]

Hi Michal,

This variant is listed as suspect by dbSNP: http://grch37.ensembl.org/Homo_sapiens/Variation/Explore?db=core;r=12:56435429-56436429;tl=7ESUIe0HqyqjbgAq-6066193;v=rs1131017;vdb=variation;vf=395694611

So by default, the VEP only reports information about the co-located variant from the HGMD database: http://grch37.ensembl.org/Homo_sapiens/Variation/Explore?db=core;r=12:56435429-56436429;tl=7ESUIe0HqyqjbgAq-6066193;v=CR1310395;vdb=variation;vf=661338393

To retrieve information from the gnomAD database, you can select the 'Include flagged variants' option in the VEP submission form.

Best wishes

Ben Ensembl Helpdesk

[michal.inbar]

Thanks! 1) Does this mean it is suspected by dbSNP for being a false positive variant in the gnomad? 2) How would I 'Include flagged variants' via the command line tool?

Answer 2

[Ben_Ensembl]

No problem.

1) The variant was flagged as suspect by dbSNP version 151, which is the dbSNP version available when using the GRCh37 Ensembl browser and VEP. The variant is not flagged as suspect in the latest version of dbSNP (dbSNP 153), which is available when using the GRCh38 Ensembl browser and VEP tool: http://www.ensembl.org/Homo_sapiens/Variation/Explore?r=12:56041645-56042645;v=rs1131017;vdb=variation;vf=95986239

So you can retrieve the GnomAD data if you use the GRCh38 Ensembl browser and VEP: http://www.ensembl.org/Homo_sapiens/Tools/VEP/Results?tl=XIKCULhlHWwEVclr-6066798

I'm not sure why dbSNP flagged this variant a suspect in version 151. It may be for a number of different reasons.

2) You can include flagged variants in the command line VEP tool by using the --failed 1 flag: http://grch37.ensembl.org/info/docs/tools/vep/script/vep_options.html#existing

[Ben_Ensembl]

You can find the number of failed variants using MySQL from the failed_variation table: http://www.ensembl.org/info/docs/api/variation/variation_schema.html#header_2

or using the Perl API: http://www.ensembl.org/info/docs/api/variation/variation_tutorial.html#failed_variants

Best wishes

Ben

[michal.inbar]

thanks again :)

I have a very large variant set and I must use GRCh37. I'm using the command line tool to annotate.

I'm not sure I want to include failed variants for the entire set because that would include the up-to-date failed variants as well. Before I dig in, perhaps you can save me the effort if you happen to have a very rough estimate of how many variants I'm dealing with? (failure status changed from 151 to 153?)