We are using the batch variant scoring function to predict the effects of promoter variants. For our analyses, we set sequence_length = 16 kb, so each variant is evaluated within a 16 kb sequence window. Our goal is to estimate the effect of a promoter variant on the closest gene, where the gene’s promoter and TSS are within the 16 kb window. We are mainly using the RNA-seq predictions for this purpose.
However, in some cases, the target gene’s full gene body extends beyond the 16 kb input window. Given this setup, we wanted to ask:
Are the raw RNA-seq scores or the quantile scores still valid for interpreting the variant’s effect on the closest gene, even if the full gene body is not contained within the 16 kb sequence window?
More specifically, should we be concerned that the RNA-seq prediction may be incomplete or biased when the promoter/TSS is inside the window but the gene body extends outside of it? In this case, is one score type, the raw score or the quantile score, more appropriate or reliable for interpretation?
Thank you very much for your guidance.