Extended Data Fig. 1. Overall burden of de novo variants in four ASD cohorts included in the discovery sample.

(A) Observed rates of de novo LoF, Dmis (REVEL > = 0.5) and silent variants (B) are compared with expected rates. We used a 7mer sequence context dependent mutation rate model⁵⁵ to calculate expected rates for different classes of de novo variants after adjusting sequencing coverage, and found a close match with observed de novo rates in control trios. The rates of de novo LoF and Dmis variants in ASD cases are significantly higher than baseline expectation and are reduced in cases with known family history. Data are presented as mean values and 95% confidence interval as error bars.