Question: Program to prioritize silent SNVs?
4
gravatar for Christian
4.3 years ago by
Christian2.7k
Cambridge, US
Christian2.7k wrote:

What tools do you recommend to predict the likely functional impact of silent SNVs (i.e. synonymous, UTR, intronic, and intergenic variants) in humans? I understand that this is much more difficult than for non-synonymous variants, but a prioritization based on sequence conservation (e.g. across closely related vertebrates) is probably sufficient as first-line approximation.

To my current knowledge, popular variant annotation tools (e.g. ANNOVAR, SnpEff/SnpSift, dbNSFP) provide (conservation) scores only for non-synonymous variants. SilVA (http://compbio.cs.toronto.edu/silva/) analyzes silent variants, but I shy away from trained classifiers because of unknown biases introduced by the training data set. I guess annotating input variants with sortable numeric conservation scores would suffice for my purpose.

EDIT: Found a recent review on this subject (Hunt RC et al., 2014; Exposing synonymous mutations), but did not spot any tool in there with a specific focus on sequence conservation.

ADD COMMENTlink modified 4.2 years ago • written 4.3 years ago by Christian2.7k
2
gravatar for Cyriac Kandoth
4.3 years ago by
Cyriac Kandoth5.2k
Memorial Sloan Kettering, New York, USA
Cyriac Kandoth5.2k wrote:

Ensembl's VEP annotator provides detailed annotations for non-coding variants, and plays well with third-party plugins that can add more information like functional impact or promoter recognition motifs. The easiest way to use it is to submit your variants to their web service, but if you have a ton of variants, or if you're uncomfortable sharing your variant calls with strangers, then you can try this short tutorial on getting it set up in offline mode.

ADD COMMENTlink modified 4.3 years ago • written 4.3 years ago by Cyriac Kandoth5.2k
1

Haven't visited VEP for a while and its great to see lots of activity around this tool. I could not find core VEP functionality that goes beyond the annotation of non-coding elements, but at least one plugin (GWAVA) appears to provide conservation scores and might be worth a try.

ADD REPLYlink modified 4.3 years ago • written 4.3 years ago by Christian2.7k
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