Table 1. Gene Burden analysis.

Number of cases (n=863) and controls (n=1,604) with rare (MAF<1%) mutations in postulated CRC genes. P-values calculated using Fishers exact test, P-values <0.05 are emboldened.

		Disruptive mutations (stop-gain, frameshift)			Damaging mutations (disruptive, predicted-damaging, splice acceptor/donors			All coding non-synonymous variants
Gene	Previously Reported	Cases	Control	PFisher	Cases	Control	PFisher	Cases	Control	PFisher
BUB1	Disruptive	0	4	0.31	1	8	0.17	18	30	0.76
BUB3	Missense	0	2	0.55	0	4	0.31	1	5	0.67
FAN1	Disruptive /Missense	0	2	0.55	15	17	0.19	32	45#	0.23
FANCM	Disruptive /Missense	5	1	0.02	23	33	0.33	51$	67$	0.06
LRP6 (BPD*)	Missense	0	0	-	6 (4)	17 (13)	0.51 (0.45)	17 (8)	37 (21)	0.67
PTPN12	Missense	0	1	1.00	6	5	0.21	12	9	0.04
RPS20	Disruptive	1	0	0.35	2	0	0.12	2	0	0.12
TP53	Missense	1	0	0.35	1	1	1.00	1	4	0.66

^*Number of variants within β-Propellor domain. All 3 variants identified by de Voer et al were within BPD.

^#Total number of variants in controls = 46; 1 sample has 2 FAN1 missense

^$Totals number of variants in cases = 52, in controls =69; 3 samples have 2 FANCM missense