Appendix 1—figure 9. Variable penetrance of highly deleterious mutations.

(A) The distribution of the number of segregating variants carried by individuals in the UK Biobank in genes with estimated hs >10% for loss-of-function (LOF). 93% of individuals carry no such LOF mutations, 6% of individuals carry one mutation, and 0.2% of individuals carry two. (B) Overlap of genes that have at least one LOF mutation segregating in the UK Biobank (among ~110K individuals who self-report no long-standing illness, disability, or infirmity; see 'Materials and methods') with (in gray) genes with estimated hs > 10% for LOF (in blue) genes with de novo mutations in individuals ascertained on severe disease (developmental disorders, congenital heart disease, autism, and epilepsy) and (in red) genes with DNMs mapped in at least two affected individuals, with at least one disease.