Table 4 Functional annotation of 22 variants associated with lung cancer risk with strong evidence using HaploReg v4.1 and PolyPhen-2.

From: Genetic predisposition to lung cancer: comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies

variant	Gene (or near gene)^ǁ	HaploReg v4.1^∫											PolyPhen-2^§
variant	Gene (or near gene)^ǁ	GERP conserved	Promoter histone marks	Enhancer histone marks	DNAse	Proteins bound	Motifs changed	NHGRI/EBI GWAS hits	GRASP QTL hits	Selected eQTL hits	RefSeq genes	dbSNP functional annotation	predicted consequence on protein function	PolyPhenscore^¶
rs1760944	APEX1		24 tissues*	14 tissues*	52 tissues*	11 bound proteins			2 hits	69 hits*	OSGEP	5′UTR
rs6495309	CHRNA3		THYM	4 tissues	THYM		7 altered		2 hits	10 hits	1.4 kb 3′ of CHRNB4
rs1126579	CXCR2		BLD	BLD			9 altered			69 hits*	CXCR2	3′UTR
rs6413432	CYP2E1		4 tissues	IPSC			8 altered			1 hit	CYP2E1	intronic
rs931794	HYKK			ESDR, SKIN, BRN			4 altered		1 hit	26 hits	AGPHD1	intronic
rs664677	ATM			BLD, FAT, LIV			4 altered			24 hits	ATM	intronic
rs402710	CLPTM1L		4 tissues	7 tissues			5 altered	1 hit^†	1 hit	1 hit	CLPTM1L	intronic
rs4646903	CYP1A1		SKIN	LNG						8 hits	241 bp 3′ of CYP1A1
rs2240308	AXIN2		22 tissues*	23 tissues*	6 tissues		Smad3		2 hits	3 hits	AXIN2	missense	benign	0
rs662	PON1	conserved	LNG*	10 tissues*					2 hits	2 hits	PON1	missense	benign	0
rs462779	REV3L	conserved					BRCA1, Nkx3		1 hit	2 hits	REV3L	missense	benign	0
rs1130409	APEX1		20 tissues*	23 tissues*	4 tissues		ZNF263			8 hits	APEX1	missense	benign	0
rs16969968	CHRNA5									32 hits*	CHRNA5	missense	benign	0.045
rs13181	ERCC2	conserved	ESDR, SKIN, SPLN	4 tissues	4 tissues			1 hit^‡	3 hits	18 hits*	ERCC2	missense	benign	0
rs4880	SOD2		24 tissues*	19 tissues*	46 tissues*	CMYC,POL2, SIN3AK20	CHD2		1 hit	29 hits*	SOD2	missense	benign	0
rs351855	FGFR4	conserved	4 tissues	15 tissues*	LIV		5 altered		2 hits	15 hits	FGFR4	missense	probably damaging	0.998
rs1052133	OGG1	conserved	BLD, SKIN	10 tissues*			GATA			5 hits*	OGG1	missense	benign	0.121
rs1042522	TP53		5 tissues	9 tissues*	LNG*		9 altered		1 hit	1 hit	TP53	missense	benign	0.083
rs2736098	TERT		10 tissues*	16 tissues*	BLD		9 altered	1 hit		1 hit*	TERT	synonymous
rs11615	ERCC1	conserved	9 tissues	21 tissues*	4 tissues	ZNF263	EBF,Mtf1		2 hits	5 hits	ERCC1	synonymous
rs2910164	MIR146A	conserved	4 tissues	8 tissues							MIR146A
rs11614913	MIR196A2	conserved	13 tissues	16 tissues*	8 tissues*		HMG-IY		1 hit	6 hits	MIR196A2

^ǁThe gene name for the SNP, locating in a respective gene, was based on the annotation of dbSNP database (https://www.ncbi.nlm.nih.gov/snp/). The near gene name for a SNP that didn’t map into a gene region but its location nearby a gene based on the annotation of dbSNP database, and we also used this nearby gene name for the SNP in our study. ^∫HaploReg v4.1: a Web server for annotation of transcription regulation for genetic variants (http://archive.broadinstitute.org/mammals/haploreg/haploreg.php). ^§PolyPhen-2: a Web server for annotation of potential effects on protein structure and function for non-synonymous SNPs (http://genetics.bwh.harvard.edu/pph2/). ^¶The PolyPhen-2 reported a score that the calculated naive Bayes posterior probability of a given mutation being damaging ranging from 0 to 1, which was also classified as benign [0, 0.15], possibly damaging (0.15, 0.85], and probably damaging (0.85, 1], respectively. *Including regulatory evidence in lung cancer cell lines/tissues or normal lung cell lines/tissues. ^†GWAS for the trait of lung cancer with a P-value at 4.0 × 10⁻⁶. ^‡GWAS for the trait of lung cancer with a P-value at 9.0 × 10⁻⁷.

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Table 4 Functional annotation of 22 variants associated with lung cancer risk with strong evidence using HaploReg v4.1 and PolyPhen-2.

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