[ensembl-dev] How duplicated variants in gnomAD v2 are handled in VEP when remapped to GRCh38?
Wallace Ko
myko at l3-bioinfo.com
Wed Feb 28 08:22:42 GMT 2024
Hello,
I found another case where the VEP result is not the same as that of the
Ensembl website. Please see if this helps your investigation.
For the GRCh38 variant 1-13260172-G-A, 3 records are observed in the VCF:
$ bcftools query -Hf '%CHROM %POS %ID %REF %ALT %AC %AN %AF\n' -r
chr1:13260172 -i 'ALT="A"'
http://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh38/variation_genotype/gnomad/r2.1.1/exomes/gnomad.exomes.r2.1.1.sites.1.liftover_grch38_no_VEP.vcf.gz
| column -ts' '
#[1]CHROM [2]POS [3]ID [4]REF [5]ALT [6]AC [7]AN [8]AF
chr1 13260172 rs4026293 G A 76892 147882 0.519955
chr1 13260172 rs200091507 G A 33 49948 0.000660687
chr1 13260172 . G A 54 191992 0.000281262
In VEP 111, gnomADe_AF=0.0002813, which corresponds to the 3rd record in
the VCF.
In Ensembl website (
https://ensembl.org/Homo_sapiens/Variation/Population?db=core;r=1:13260172-13260172;v=rs1553173632;vdb=variation;vf=52479317),
it shows that AF for allele A is 0.520, which corresponds to the first
record in the VCF.
Regards,
Wallace Ko
On Tue, Feb 27, 2024 at 5:32 PM Wallace Ko <myko at l3-bioinfo.com> wrote:
> Hello Ensembl Team,
>
> Some variants in GRCh37 can be remapped to the same location in GRCh38.
> E.g. 1-13497572-G-A (
> https://gnomad.broadinstitute.org/variant/1-13497572-G-A?dataset=gnomad_r2_1)
> and 1-13718406-G-A (
> https://gnomad.broadinstitute.org/variant/1-13718406-G-A?dataset=gnomad_r2_1)
> in GRCh37 are both remapped to 1-13391946-G-A in GRCh38 according to gnomAD
> webpages.
>
> From the gnomAD v2 VCF in Ensembl FTP, both records are observed:
>
> $ bcftools view -Ou
> http://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh38/variation_genotype/gnomad/r2.1.1/exomes/gnomad.exomes.r2.1.1.sites.1.liftover_grch38_no_VEP.vcf.gz
> -i 'ALT="A"' chr1:13391946-13391946 | bcftools query -f '%CHROM
> %POS %ID %REF %ALT %AC %AN %AF\n'
> chr1 13391946 rs199881782 G A 6177 85026 0.0726484
> chr1 13391946 rs200047809 G A 72 211396 0.000340593
>
> From VEP 111, I obtained gnomADe_AF=0.0003406 for this variant.
>
> I wonder how VEP determines to report the AF of rs200047809, instead
> of rs199881782 or arithmetic mean of both.
>
> Regards,
> Wallace Ko
>
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