Vep loftool threshold

Question

[BAGeno]

Hi,

I have annotated my file with vep loftool. I want to find out what is threshold used by vep loftool to assign variants as probably damaging, possibly damaging or benign? I know that more lower score more intolerant s variant is but what is criteria to rank variants. Also I want to know that is loftool used to predict loss of function variants in brain diseases or it can be used for some disease as well?

Answer 1

[Emily]

LoFtool only provides a score for the gene, based on the ratio of known loss-of-function to synonymous variants in that gene. It does not give you a qualitative prediction. Those terms look like the ones used by PolyPhen-2.

[BAGeno]

I want to separate probably damaging variants from output. So what value should I used to separate these variants?

[Emily]

You can get a number of pathogenicity predictors from the VEP, including SIFT, PolyPhen-2, CADD, MutationAssessor, REVEL and MetalR. You can use the qualitative predictions that come with all/any of these to filter. Remember that they are predictions, usually based on things like protein conservation between species, chemical changes in amino acids and position of protein domains, and do not tell you the actual impact on protein function.