Filtering for affinity-optimizing (aff-opt) SNVs significantly increases our ability to predict causal GOF enhancer variants. The bar graph shows the percentage of all SNVs that lead to GOF expression relative to the percentage of affinity-optimizing SNVs that lead to GOF expression. Green bars indicate SNVs that cause GOF expression within analysed MPRA datasets; yellow bar indicates SNVs that cause GOF expression in our the current study—namely, French 2 and Indian 2. Fisher’s exact test was used to determine any significant enrichment for GOF expression in the all and aff-opt categories: ** P < 0.001, * P < 0.01. Affinity-optimizing SNVs are those that lead to a fold change of at least 1.6 for ETS because this is the fold change for French 2, Indian 2 and Syn 0.25. Affinity-optimizing SNVs for AP-1 and IRF are those that cause a fold change of at least 1.5.
