Question: How to judge severity of variants in genes
gravatar for mschmid
4.7 years ago by
mschmid150 wrote:

I did some variant calling on a 9MB genome we assembled and compared to another genome. We just got a few SNPs and single nucleotide indels.

With SnpEff I assessed the severity of the variants. We just got a few indels in genes.

Interestingly most of the indels are close to the stop codon. And most of them are in areas where we did not find known motifs with InterProScan...

I want to further assess the severity of the indels which are in genes. Any papers or other suggestions?

It is realy interesting that I see a strong bias of indels towards the end of the genes. Did you ever observe the same picture?

variants snp annotation • 1.3k views
ADD COMMENTlink modified 4.4 years ago by mkulecka310 • written 4.7 years ago by mschmid150
gravatar for Michael Schubert
4.7 years ago by
Cambridge, UK
Michael Schubert7.0k wrote:

There are plenty of tools out there that try to assess the impact of different mutations (including indels) in proteins.

Have a look at VEP

The VEP determines the effect of your variants (SNPs, insertions, deletions, CNVs or structural variants) on genes, transcripts, and protein sequence, as well as regulatory regions. Simply input the coordinates of your variants and the nucleotide changes to find out the [...]


ANNOVAR is an efficient software tool to utilize update-to-date information to functionally annotate genetic variants detected from diverse genomes (including human genome hg18, hg19, hg38, as well as mouse, worm, fly, yeast and many others). Given a list of variants with chromosome, start position, end position, reference nucleotide and observed nucleotides, ANNOVAR can perform [...]

ADD COMMENTlink modified 7 months ago by RamRS27k • written 4.7 years ago by Michael Schubert7.0k

Thanks Michael! Unfortunately, you not really answered my question. I was more asking if it is possible to asses the severity of a indel based on its position on a CDS. Or if there is any resources out there. I do not have much knowlegede about that.

Also, I would be interested if it is normal that the indels occur more to the end of a CDS. Did anyone ever see such a bias?

ADD REPLYlink written 4.7 years ago by mschmid150

Unless I understand something wrong, the "severity" you are looking for is functional impact. This is exactly what the tools above do. I am not aware of any systematic bias if short indels closer to the stop codon as opposed to other segments of the gene.

ADD REPLYlink written 4.7 years ago by Michael Schubert7.0k
gravatar for Jeremy Schwartzentruber
4.4 years ago by
Wellcome Trust Sanger Institute, Cambridge, UK

One reason you might find indels in the last exon of genes is that they are much less likely to lead to nonsense-mediated decay, in the case that they are frame-shifting indels.

How  many genes are you talking about?  If you have other organisms to compare to, you could look at the conservation across those genes. It might be that you are just looking at poorly-conserved regions.

Have you checked whether the indels are occurring in repetitive sequence, e.g. poly-A or poly-Q repeats? Replication errors at such sites often lead to short (in-frame) indels that are less likely to affect protein function.


ADD COMMENTlink written 4.4 years ago by Jeremy Schwartzentruber20
gravatar for mkulecka
4.4 years ago by
European Union
mkulecka310 wrote:

For simple check of deleteriousness in silico I strongly recommend CADD - it provides you with a lot of annotations and can be used for more than one type of variant. For indels only there's SIFT Indel: . 

ADD COMMENTlink written 4.4 years ago by mkulecka310
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