Skip to main content
. 2018 Dec 12;10(12):511. doi: 10.3390/cancers10120511

Table 5.

Prioritized variants for the validation phase.

Gene HGVS Coding HGVS Protein Classification in Annovar 1 Rs ID ClinVar DFS 2 Response 2 Function 3 AF 4 ExAC 5 NCMG 6
ABCA4 c.5603A>T p.N1868I NS rs1801466 likely benign 0.03 D; CADD 0.105 0.066 0.065
ABCB1 intronic rs2032583 0.03 PA166157317 0.106 0.123 0.093
ABCB5 intronic rs11983326 0.04 0.038 DFS & response 0.279 0.297 0.246
ABCB8 intronic rs3214587 0.01 miR-670-3p 0.115
ABCC1 c.*1512T>C UTR3 rs212091 0.05 PA166154987 0.180 0.114
ABCC1 c.*543C>T UTR3 rs3743527 0.05 PA166155049 0.205
ABCC3 intronic rs4148413 0.002 1f, PINES 0.168
ABCC6 c.2835C>T p.P945P synonymous rs2856585 pathogenic 0.03 ClinVar 0.064 0.099 0.044
AHRR intronic rs2013782 0.02 1f 0.587 0.623 0.597
AKR7A2 c.424G>A p.A142T NS rs1043657 0.01 PA166161794; CADD 0.095 0.093 0.081
AKT1 intronic rs3803304 0.05 PA166154802; 1f 0.292 0.289
ATP7A c.2299G>C p.V767L NS rs2227291 benign 0.003 PA166157866 0.260 0.217 0.225
BAK1 dist = 114 downstream rs210134 0.033 1f, PINES 0.750
BIRC7 c.528C>T p.S176S synonymous rs2273487 <0.001 1b 0.486 0.467 0.464
BLK c.-53667C>T UTR5 rs922483 benign 0.023 1f 0.229
CDA c.79A>C p.K27Q NS rs2072671 0.01 PA166153667 0.362 0.343 0.296
CES1 c.-75T>G UTR5 rs3815583 0.038 PA166155058 0.202 . 0.162
CES1 c.224G>A p.S75N NS rs2307240 0.01 PA166155039 0.067 0.054 0.063
CES1 intronic rs76336259 0.001 0.046 DFS & response 0.063 0.060
CMPK1 c.22G>C p.G8R NS rs7543016 0.05 PA166153793 0.451 0.538 0.320
CYP2C9 intronic rs1934969 0.03 PA166153986 0.613 0.658
CYP2D6 c.100C>T p.P34S NS rs1065852 likely benign 0.021 PA166156062; PharmVar 0.214 0.249 0.206
CYP2D6 c.985 + 39G>A ncRNA_intronic rs28371725 0.011 PA166156155 0.059 0.095 0.084
CYP2E1 c.1263T>C p.F421F synonymous rs2515641 benign 0.03 PA166154017 0.856 0.887 0.880
CYP2E1 intronic rs2070677 0.05 1f 0.856 0.867
CYP4F12 intronic rs12460651 0.02 0.029 DFS & response 0.882
DFFB intronic rs4376673 0.04 0.047 DFS & response; PINES 0.909 0.947 0.901
DPYD c.2194G>A p.V732I NS rs1801160 likely_benign 0.02 PA166153647 0.052 0.047 0.045
DPYD c.1896T>C p.F632F synonymous rs17376848 likely_benign 0.03 PA166153874; CADD 0.057 0.037 0.047
DPYD c.496A>G p.M166V NS rs2297595 drug_response PA166153696; D 0.148 0.103 0.125
DPYS intronic rs2669429 not_provided 0.01 PA166157579 0.540 0.557
ENOSF1 intronic rs2612083 0.01 1f 0.381 . 0.322
EPHX2 c.662G>A p.R221Q NS rs751141 risk_factor 0.03 sequence in silico tools set 0.114 0.095 0.115
EPHX2 dist = 55 downstream rs4149259 0.03 1f 0.167
ESR2 c.*39G>A UTR3 rs4986938 0.05 PA166154805 0.371 0.379 0.347
GSTA1 c.-9630T>C UTR5 rs3957357 0.047 PA166157094 0.591
GSTA2 c.335G>C p.S112T NS rs2180314 0.017 PA166157020 0.592 0.590 0.581
GSTP1 c.313A>G p.I105V NS rs1695 drug_response 0.05 PA166154249 0.329 0.319 0.320
GSTP1 intronic rs762803 <0.001 1f; PINES 0.386 0.406 0.323
IRS1 c.*4476A>G UTR3 rs2288587 0.05 1f 0.057
KCNAB1 intronic rs2293194 0.04 0.013 DFS & response 0.476 0.515
MADD intronic rs10501320 0.05 IW; PINES 0.281
NR5A2 dist = 45 upstream rs2816948 0.05 0.036 DFS & response; PINES 0.130
PIK3C2G c.2732C>T p.P911L NS rs12312266 0.04 sequence in silico tools set 0.205 0.298 0.242
PIP4K2B intronic rs2075061 0.02 1f 0.605 0.592
PPARA c.*5977G>A UTR3 rs9626814 0.019 1d 0.101 .
PPARG c.1347C>T p.H449H synonymous rs3856806 likely_benign 0.046 PA166156388 0.120 0.125 0.133
RALBP1 c.*756G>A UTR3 rs3322 0.03 1f 0.095 0.092 0.072
RARB c.*1287T>G UTR3 rs1058378 0.013 IW, miR-665 0.091 0.083
RPTOR c.90T>C p.F30F synonymous rs61750765 0.03 IW 0.238 0.126 0.142
RRAGD c.*1105T>A UTR3 rs1555403 0.019 1f 0.238 .
SLC22A1 c.1222A>G p.M408V NS rs628031 0.028 PA166156933 0.600 0.592 0.605
SLC28A3 c.338A>G p.Y113C NS rs10868138 0.022 PA166157820 0.067 0.085 0.091
SLC2A1 c.*462G>C UTR3 rs4658 benign 0.01 PA166153544 0.210 0.178
SLCO1A2 c.-189_-188insA UTR5 rs3834939 0.05 PA166163600 0.295
SLCO1C1 intronic rs34288910 0.03 0.028 DFS & response 0.144 0.128 0.152
TUBB1 c.*817G>C UTR3 rs10485828 0.03 PA166155965 0.212
UGT2A1 c.949G>A p.G317R NS rs4148301 0.033 sequence in silico tools set 0.110 0.096 0.104

Validated variants (Section 2.2.2.) in bold. Variants rs3815583, rs1065852, and rs3322 were excluded due to technical failure. Footnotes: 1 NS = non-synonymous; 2 p-value provided for clinical associations; 3 Prediction based on combination of pharmacogenomic databases, e.g., PharmGKB (“PA” designation stands for specific diseases, genes and drugs in the database) and in silico individual tools, e.g., TargetScan (micro RNA target prediction), metaLR and metaSVM (D = deleterious), CADD (cut-off value ≥ 19), Nexus IW score under 0.01 (IW), PINES (p-value ≤ 0.05) or Regulome DB (score provided), and sequence in silico tools set (see Section 4 Materials and Methods and data provided in Table S4); 4 AF = non-reference allelic frequencies in the testing set; 5 Exome Aggregation Consortium (ExAc), allelic frequencies in European non-Finnish population; 6 National Center for Medical Genomics (NCMG), allelic frequencies in general Czech population.