Table 1.

Variants with a worldwide allelic frequency of <1% that were detected in our material more than once. EMAF: European minor allele frequency; ExAC ENFAF: ExAC European non-Finnish allele frequency; nl-C1-INH-HAE AF: allele frequency among nl-C1-INH-HAE patients; C1-INH-HAE AF: allele frequency among C1-INH-HAE patients, P1: EMAF vs. nl-C1-INH-HAE AF, P2: EMAF vs. C1-INH-HAE AF, P3: ni-C1-INH-HAE AF vs. C1-INH-HAE AF.

Genes	Coding	Amino Acid Change	dbSNP	SIFT	PolyPhen	EMAF	ExAC ENFAF	nl-C1-INH-HAE AF	C1-INH-HAE AF	P1	P2	P3
BDKRB1	c.721G>A	p.Gly241Arg	rs45528332	tolerated	probably damaging	0.0037	0.0052	0.0113	0.0148	0.1500	0.0350	0.7000
MME	c.674G>C	p.Gly225Ala	rs147564881	tolerated	probably damaging	0.0023	0.0033	0.0113	0.0030	0.0310	0.7400	0.2100
PLAUR	c.802A>G	p.Met268Val	rs138492321	tolerated	possibly damaging	0.0062	0.0045	0.0188	0.0000	0.0440	0.1500	0.0110
C1S	c.943G>A	p.Asp315Asn	rs117907409	deleterious	probably damaging	0.0053	0.0052	0.0113	0.0059	0.2400	0.8300	0.4700
F13B	c.1025T>C	p.Ile342Thr	rs17514281	deleterious	possibly damaging	0.0097	0.0098	0.0263	0.0059	0.0380	0.4900	0.0390
F2	c.*97G>A		rs1799963			0.0080		0.0263	0.0148	0.0130	0.2600	0.3100
TLR4	c.842G>A	p.Cys281Tyr	rs137853920	deleterious	probably damaging	0.0044	0.0027	0.0150	0.0030	0.0420	0.7900	0.1000
KRT1	c.1669A>G	p.Ser557Gly	rs77846840	tolerated	benign		0.0019	0.0263	0.0296			0.8000
SERPINE1	c.*180C>T		rs41334349			0.0110		0.0226	0.0266	0.1400	0.0400	0.7500
AR	c.-207C>A		rs189146053			0.0000		0.0188	0.0030	<0.0001	0.0844	0.0500
AR	c.1174C>T	p.Pro392Ser	rs201934623	tolerated	benign	0.0000	0.0041	0.0113	0.0000	0.0007		0.0500
TPSAB1	c.407A>G	p.His136Arg	rs201820654	tolerated	benign		0.0034	0.0113	0.0089			0.7600
TPSG1	c.508G>A	p.Gly170Arg	rs117769620	tolerated	benign	0.0065	0.0073	0.0188	0.0118	0.0757	0.3893	0.4832
ELANE	c.770C>T	p.Pro257Leu	rs17216663	tolerated	benign	0.0108	0.0080	0.0188	0.0030	0.3062	0.1775	0.0530
F12	c.418C>G	p.Leu140Val	rs35515200	tolerated	possibly damaging	0.0042	0.0033	0.0075	0.0030	0.4533	0.7904	0.4287
F12	c.530C>T	p.Ala177Val	rs144821595	tolerated	benign	0.0002	0.0001	0.0075	0.0000	<0.0001	0.7948	0.1103
ACE	c.1453C>G	p.Pro485Ala	rs202178737	deleterious	benign	0.0000	0.0001	0.0075	0.0000	0.0059		0.1103
BDKRB1	c.844C>T	p.Arg282Ter	rs145322761			0.0035	0.0038	0.0075	0.0030	0.4533	0.7904	0.4287
PLG	c.266G>A	p.Arg89Lys	rs143079629	tolerated	benign	0.0100	0.0108	0.0075	0.0030	0.7164	0.2177	0.4287
KLK3	c.629C>G	p.Ser210Trp	rs61729813	deleterious	probably damaging	0.0110	0.0109	0.0075	0.0178	0.6223	0.3319	0.2748
DPP4	c.796G>A	p.Val266Ile	rs56179129	tolerated	benign	0.0060	0.0045	0.0075	0.0000	0.7755	0.1547	0.1103
PLAU	c.1048T>C	p.Tyr350His	rs72816325	deleterious	probably damaging	0.0058	0.0059	0.0075	0.0000	0.7755	0.1547	0.1103
PLAUR	c.-87C>T		rs147665588			0.0060		0.0075	0.0089	0.7755	0.5702	0.8550
F13A1	c.1730C>T	p.Thr577Met	rs143711562	tolerated	benign	0.0029	0.0020	0.0075	0.0000	0.2930	0.3149	0.1103
TNF	c.251C>T	p.Pro84Leu	rs4645843	tolerated	benign	0.0030	0.0028	0.0075	0.0030	0.2930	0.9945	0.4287
GPER1	c.14C>T	p.Ser5Phe	rs117290655	tolerated	benign	0.0048	0.0045	0.0075	0.0089	0.6173	0.4193	0.8550
MPO	c.2031-2A>C		rs35897051			0.0072	0.0071	0.0075	0.0059	0.9227	0.8391	0.8096