Fig. 3.

Increased enrichment for rare variants at high CADD scores. CADD assigns higher scores with increasing population frequency, despite allele frequency not being included in the model. Here, depletion and enrichment of variants is grouped by frequency and CADD score percentiles, with CADD-Splice outperforming previous versions. At high CADD scores, frequent (MAF > 0.001) and rare (allele count > 1) variants are depleted and singletons (observed once in gnomAD) enriched. For variants in canonical splice sites (left), the difference is mostly within the bootstrapped 95%-confidence interval, but CADD-Splice significantly outperforms previous versions within 20 bp of splice sites (right)