Functional Relevance Of Stop Retained Variants?

Question

[Rubal7]

Hello Everyone,

I am looking for functional variants in population genomic data. I have identified a candidate variant (high frequency and highly conserved across mammals). The variant is classified by VEP as a stop retained variant, meaning that "A sequence variant where at least one base in the terminator codon is changed, but the terminator remains". Does anyone know of any cases where such a variant has been associated with phenotype variation of any kind? I am wondering if such a variant is only as likely to be functional as any other synonymous variant, or if being in the terminator codon is associated with any increased chance of having a functional effect. If anyone has any experience or ideas on this or a reference to a paper with a functional variant of this kind that would be great. So far I haven't found any examples.

Thanks in advance, Rubal

Answer 1

[Emily]

If such a variant does cause a phenotype I would assume that is part of a regulatory region, not due to changes in the stop codon.

[Rubal7]

Could you expand a little on what you mean, I am a little unclear how a synonymous change in a stop codon can be classified as a regulatory region? Thanks very much, probably just my confusion

[Emily]

There might be a regulatory region that overlaps the stop codon.