pLOF variants were identified using Loss Of Function Transcript Effect Estimator (LOFTEE) v.0.3-beta85 and Variant Effect Predictor (VEP) v.9486. The genomic coordinates of coding elements were based on GENCODE v.2915. Only stop-gained, frameshift and splice-site-disturbing variants annotated as high-confidence pLOF variants were used in the analysis. The pLOF variants with allele frequency > 0.5% or within regions masked due to poor accessibility were excluded from analysis (see Supplementary Information 1.5 for details).
