Motif score change in VEP(Ensembl)

Question

[Inbalor]

I am using VEP from Ensembl to see if SNPs identified can disturb a transcription factor binding site. Based on VEP analysis you get a motif score change that is the differences between one allele and the other.

I don't understand the score I obtained. Furthermore, I don't know how to interpret differences, what is the difference to think that the SNP could have an impact on the transcription binding site? My biggest differences is -0.035.

Thanks in advance for helping me in understanding it better.

Answer 1

[Emily]

The motif scores are between 0 and 1. It indicates how strong a binding site it is for the transcription factor, with 1 the best and 0 the worst. The score change indicates whether the score increases or decreases and by how much as a result of the SNP. Another, possibly more useful, measure is the High Info Position, that tells me whether the SNP changes a base which is vital to the motif function or not.

Here's an example SNP. If I run it through VEP, I see that it is at a high info position and gives a score change of -0.085. If I go to the browser to the position of that motif, I can see the SNP (blue R in the middle), which corresponds to a T on the reverse strand. The motif page shows me the motif. The mutated base is the big T in the middle, which, from the frequency scores, is clearly the most common base at that position in this motif, and changing it would be likely to affect TF binding, hence it being labelled a high info position and the relatively high score change of -0.085.

[Inbalor]

Thanks a lot for your explanation. It definitely answers my question.