Finding genes/proteins from variant files

Question

[deepti1rao]

After getting a variant file and using a software like VEP or snpEff to annotate variants, I want to look up ensembl for validating the presence of frameshift variants that may be contributing towards a phenotype. Instead of studying each predicted variant manually, by checking if a locus has a gene and the variant is within the gene, do I have a better option of generating a file containing the gene/protein information for each of the entries in my vcf or annotation file? How can I do this??

[cpad0112]

VEP and snpEff both will give affected gene and protein information and also predicted clinical significance.

[cschu181]

With "clinical significance" do you mean the amino acid change (in case of CDS mutations) or some statistical significance calculation?

[cpad0112]

Words to be high lighted are: predicted clinical significance, not clinical significance. Predicted clinical significance from polyphen and sift. Refer to Protein function predictions section in http://grch37.ensembl.org/info/genome/variation/predicted_data.html. Something like this:

Tool    Encoded value   Qualitative prediction
PolyPhen    0   "probably damaging"
PolyPhen    1   "possibly damaging"
PolyPhen    2   "benign"
PolyPhen    3   "unknown"
SIFT    0   "tolerated"
SIFT    1   "deleterious"

[Kevin Blighe]

cpad's comments are good but, just to be aware, there are in fact >60 different in silico prediction tools out there, many that can now provide functional significance for non-coding variants: A: pathogenicity predictors of cancer mutations