[ensembl-dev] VEP maf problems with certain variants

[Wolf Beat]

Hello,

i stumbled uppon an issue i don't really know how to solve right now.

When looking at rs4784677:
http://grch37.ensembl.org/Homo_sapiens/Variation/Explore?r=16:56548001-56549001;v=rs4784677;vdb=variation;vf=105727621

We see an MAF of < 0.01 and its pathogenic.
The Variant is C>T.

Then we look at clinvar for this variant:
http://www.ncbi.nlm.nih.gov/clinvar/variation/4576/

The same variant, but now its C>C, looks like some reference problem/mismatch.

Looking at exac:
http://exac.broadinstitute.org/variant/16-56548501-C-T

We get an MAF of 0.9938, so its clearly a reference sequence problem.

The problem arrises now when using VEP:

http://grch37.rest.ensembl.org/vep/human/id/rs4784677?content-type=application/json

There we find:
"minor_allele_freq":0.0036
"allele_string":"C/T"
as well as:
"minor_allele":"C"
"exac_allele":"T"
"exac_maf":0.994

So both the "general" maf and the exac maf seem to talk about the same rs number, but in reality they are not.

How do i solve this? Can i solve this? Its not the first time i have seen this but i never really investigated the reasons before.

Should i take the higher MAF between the two? Should i take the exac one? I'm afraid by using such a workaround i will just run into trouble elsewhere where the situation is reversed.

Thank you for your help

Kind regards

Beat Wolf