The supporting evidence for this likely functional SNV (rs117480515) is detailed in Figure 4A. A set of immune-associated proteins are shown by ChIP-seq to bind regions overlapping this SNV: NFKB, BCL11A, BCLAF1, EBF1, MEF2A, and MEF2C (Fig. 4B,C). However, there is only one putative binding site (based on PWMs) overlapping this SNV and that belongs to the BCL family, indicating that BCL binding is disrupted by this polymorphism. In fact, the actual TT>A polymorphism decreases the information content match to the BCL consensus site by 3.24 bits and moves it below our PWM call threshold. The study authors demonstrate a decrease in NFKB binding with the polymorphism and conclude that this variant is likely to influence TNFAIP3 expression by decreasing factor binding in response to pro-inflammatory signals. However, in our analysis, any NFKB binding sites are intact, and we find it likely that the actual cause of the binding disruption is due to a BCL motif disruption. It is possible that BCL binding assists NFKB binding at this genomic location.
