Fig. 4

Rare SVs are enriched for hallmarks of deleterious biological outcomes. Comparing all rare (VF < 1%) and common (VF > 1%) SVs discovered in this cohort revealed differences in their respective functional annotations (Additional file 2: Table S2). a Rare SVs were larger on average than common SVs [1]. b Rare SVs were more likely than common SVs to disrupt genes, particularly when the disruption was predicted to result in LoF. Rare SVs were also more likely than common SVs to result in disruption of promoters [112, 114], enhancers [112, 114], and TAD boundaries [110]. c Genes predicted to harbor at least one LoF mutation due to a rare SV were enriched in many subcategories when compared to common SV, including genes predicted to be constrained against truncating mutations in healthy individuals (Constrained) [65, 66], genes predicted to be intolerant of functional variation in healthy individuals (Intolerant) [67], genes with significant burdens of exonic deletions in NDD cases versus healthy controls (NDD ExDels) [38], genes associated with an autosomal dominant disorder (Autosomal Dom.) [68, 69], and genes with at least one pathogenic variant reported in ClinVar (Disease Assoc.) [70] (Additional file 2: Table S3)