terms of allele frequency (from private up to a maximum of 5%), predicted consequence (for example, PTV or missense), and REVEL and MTR scores. On the basis of SnpEff annotations, we defined synonymous variants as those annotated as ‘synonymous_variant’. We defined PTVs as variants annotated as exon_loss_variant, frameshift_variant, start_lost, stop_gained, stop_lost, splice_acceptor_variant, splice_donor_variant, gene_fusion, bidirectional_gene_fusion, rare_amino_acid_variant, and transcript_ablation. We defined missense as: missense_variant_splice_region_variant, and missense_variant. Non-synonymous variants included: exon_loss_variant, frameshift_variant, start_lost, stop_gained, stop_lost, splice_acceptor_variant, splice_donor_variant, gene_fusion, bidirectional_gene_fusion, rare_amino_acid_variant, transcript_ablation, conservative_inframe_deletion, conservative_inframe_insertion, disruptive_inframe_insertion, disruptive_inframe_deletion, missense_variant_splice_region_variant, missense_variant, and protein_altering_variant.
