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SACGF / variantgrid

VariantGrid public repo
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Warn when variant ref doesn't match our reference fasta #68

Open davmlaw opened 4 years ago

davmlaw commented 4 years ago

A CCB researcher emailed about how 17:7574012 G>A has HGVS of ENST00000269305.4:c.1015G>T

As it's -'ve strand you'd think given the ref G would be complement C ie HGVS should be ENST00000269305.4:c.1015C>T

It looks like VEP calculates HGVS using the fasta reference base, this kind of makes sense (due to normalization and annotations etc) but I have raised an issue with them to make it more explicit in their documentation: https://github.com/Ensembl/ensembl-vep/issues/865

In the mean time, I think we should definitely add a warning about the reference base being different than our Fasta and what that means. We could initially use PyHGVS and long term modify our annotation to add a CHECK_REF option which we can display a warning about on the variant details page:

https://asia.ensembl.org/info/docs/tools/vep/script/vep_options.html#dont_skip

Combining --check_ref with --dont_skip will add a CHECK_REF output field when the given reference does not match the underlying reference sequence.

davmlaw commented 5 months ago

Not that hard to read bcftools output:

REF_MISMATCH    NC_000017.10    7676584 G   C