Ensembl Ref/alt allele discrepancy

Question

[patelk26]

Hello,

While exploring rs72552763 INDEL in Ensembl, the Alleles field show the ref and alt allele as ATGAT/AT. However, in the following line that provides location, the VCF shows ref and alt allele as ATGA A

Why is there a discrepancy in ref/alt alleles? I am not sure if I am missing something obvious here. Any help to understand this discrepancy will be highly appreciated!

Thank you very much!

Answer 1

[Ben Moore]

Hi patelk26 - this is just two different ways of representing the inframe deletion of 'TGA' according to either the Ensembl default or VCF specifications: https://www.ensembl.org/info/docs/tools/vep/vep_formats.html#input

[patelk26]

Thank you for your prompt response. This is a naive question. I get confused because when I look at dbSNP record, it indicates the bases GAT are deleted, unless I am interpreting the record incorrectly. Could you please help clarify this? Thanks again!

Answer 2

[Zhenyu Zhang]

It's both an ATG deletion and a GAT deletion. This is essential a variant normalization issue. However, when GAT is used, the coordinate should change. So I assume 2nd report you posted is wrong.

[patelk26]

Thank you for your comment. I guess this add more to my confusion. Is it an TGA/GAT deletion like Ben_Ensembl suggested, or ATG deletion?

[Ben Moore]

As Zhenyu Zhang said, this is a variant normalisation issue. For example, you could remove 'ATG', 'TGA' or 'GAT' from 'ATGAT' and be left with 'AT'. Different variant notation formats have different ways of dealing with this ambiguity, for example, VCF describes variants using their most 5’ representation, while HGVS format describes a variant at its most 3’ location.

[Mwangana]

@Ben_Ensembl: Searching for POS 160139849 in the reference panel on this link http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/data_collections/1000G_2504_high_coverage/working/20220422_3202_phased_SNV_INDEL_SV/1kGP_high_coverage_Illumina.chr6.filtered.SNV_INDEL_SV_phased_panel.vcf.gz returns a variant with a POS of 160139848 and, REF and ALT as CATG and C, respectively. Is this the same variant?