SNP deleterious or tolerated? (VEP tool)

[clarissaboschi]

Dear members

I used VEP (Variant Effect Predictor) tool to annotate SNPs. I used the option "--sift b" to obtain SIFT scores, such as tolerated or deleterious SNPs.

From the SIFT paper, they recommend "Deleterious (sift<=0.05) and tolerated (sift>0.05)."
But in other paper they considered one SNP tolerated with SIFT score = 0.05


From my the VEP results I had SNPs tolerated with SIFT score = 0.05 and also SNPs with deleterious effect with 0.05 score. This is correct?
I am confusing! A SNP with SIFT score = 0.05 is deleterious or tolerated?????

thanks
Clarissa

[Elsie]

From http://sift.jcvi.org/www/SIFT_help.html

SIFT takes a query sequence and uses multiple alignment information to predict tolerated and deleterious substitutions for every position of the query sequence. SIFT is a multistep procedure that (1) searches for similar sequences, (2) chooses closely related sequences that may share similar function to the query sequence , (3) obtains the alignment of these chosen sequences, and (4) calculates normalized probabilities for all possible substitutions from the alignment. Positions with normalized probabilities less than 0.05 are predicted to be deleterious, those greater than or equal to 0.05 are predicted to be tolerated.

[clarissaboschi]

Hi Elsie
Thanks for your reply, I know that (I read the SIFT paper).

But why VEP tool is classifying some SNPs with 0.05 sift score as tolerated and others as deleterious??

example
chr1_1102 A ENSGALG00000001981 ENSGALT00000003085 missense_variant 764/2316 tTc/tAc SIFT=tolerated(0.05)

chr1_1116 T ENSGALG00000006119 ENSGALT00000009874 missense_variant 146/1407 tCt/tAt SIFT=deleterious(0.05)

[happy1979]

Hi Everybody,
I am sorry to ask this question here, as I looked for how to post a new subject but I didnt find any so I write here.
I have to work with UCSC genome browser and have to answer the below questions, does anyone can help me ?

how can calculate below points for HoxA1- A13 by UCSC browser?

1) Common SNPs (138) cumulative length

2) Common SNPs (138) % of Cluster

3) Repetitive Content cumulative length

4) Repetitive Content % of cluster

The same I have to do for the relevant chromosome, I mean as HoxA cluster is on chromosome 7, I should answer the same questions for the chromosome.

Thanks

[Elsie]

clarissaboschi - no idea sorry, I'd suggest contacting the VEP authors directly with a reproducible/detailed example - good luck.