F7 Common Variants (Polymorphisms)
| Variant ID | Name | Type | Effect | Location | cDNA Change | Protein Change | Cases Reported | MAF* | Legacy Nomenclature | Comments | Known Phenotypic effect | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| In vivo | In vitro | |||||||||||
| 992 | rs510317 | Point | Promoter | Flanking (5') | c.-402A>G | 1 | 0.2326 | NA | Comparison of PrASE and Pyrosequencing for SNP Genotyping | The rare c.-402A allele was associated with significantly higher FVII:C and FVII:Ag levels than subjects homozygous for the common c.-402G allele (p<0.05) (16038716)" | The rare c.-402A allele confers increased transcriptional activity and is associated with increased plasma FVII:C level (10233895). The allelic variant c.-402A showed a statistically significant increase in expression levels (increase of 50.99%) (17292373)" | |
| 991 | rs510335 | Point | Promoter | Flanking (5') | c.-401G>T | 1 | 0.2041 | NA | In complete allelic association with c.-325_-324ins10 and c.-122C | No variant-specific in vivo studies as the c.-401T variant is in complete association with c.-325_-324ins10 (10233895)" | The allelic variant c.-401T showed an increase of 39.04% when analyzed alone. By contrast, this effect disappeared when combined with c.-325_-324ins10 (17292373)" | |
| 996 | rs5742910 | Insertion | Promoter | Flanking (5') | c.-325_-324insCCTATATCCT | 81 | 0.23 | WT=A1: Var = A2 | In linkage disequilibrium with p.(Arg413Gln) | Genetic variation associated with the c.-325_-324ins10 polymorphism contributes to 26% and 23% of the variance of FVII:C and FVII:Ag respectively (8548429)" | Decanucleotide insert at c.-325 is shown to reduce promoter activity by 33% compared with wild type (reporter gene constructs in HepG2) (8576177). This was confirmed in both individual and combined allelic variants experiments) (17292373) | |
| 995 | rs561241 | Point | Promoter | Flanking (5') | c.-122T>C | 6 | 0.1436 | WT=P1: Var=P2 | In complete allelic association with c.-325_-324ins10 and c.-401T (possible exceptions) | No in vivo studies as the c.-122C variant is in complete association with c.-325_-324ins10 | The allelic variant c.-122C caused a statistically significant reduction in expression level at 39.90% (reporter plasmids containing individual allelic variant) (17292373)" | |
| 993 | rs6039 | Point | Intronic | Intron (1) | c.64+9G>A | 7 | 0.1403992 | G73A (DNA numbering): WT=G1: Var=G2 | In linkage disequilibrium with p.(Arg413Gln) | Due to the linkage disequilibrium, they could not establish whether the c.64+9G>A allele variant contributed per se to lowering FVII:C levels study (10691850)" | There is no in vitro study | |
| 999 | rs6042 | Point | Silent | Exon (6) | c.525C>T | p.(His175=) | 64 | 0.1345885 | H115=: WT=H1 (or C1): Var=H2 (or C2) | |||
| 988 | VNTR[8] | Indel | Intronic | Exon (8) | c.795_805+26[8] | 1 | NA | VNTR[6] is the Wild Type | Due to the low frequency of this allele, no large studies were published. Subjects carring an H8 allele showed a high FVIIa level | A quantitative analysis of transcripts indicated a parallel decrease of the IVS7 repeat number and mRNA relative expression (VNTR[6] being considered as a reference). VNTR[8] showed higher values than VNTR[6] (10828024)" | ||
| 989 | VNTR[5] | Indel | Intronic | Exon (8) | c.795_805+26[5] | 0 | NA | VNTR[6] is the Wild Type | Due to the low frequency of this allele, no large studies were published. Subjects with the H5 allele (without c.-325ins10 neither p.413Gln) showed lower FVII levels than controls. | A quantitative analysis of transcripts indicated a parallel decrease of the IVS7 repeat number and mRNA relative expression (VNTR[6] being considered as a reference). VNTR[5] showed lower values than VNTR[6] (10828024)" | ||
| 990 | VNTR[7] | Indel | Intronic | Exon (8) | c.795_805+26[7] | 89 | 0.31 | Var=a (7) or h7 | VNTR[6] is the Wild Type | Genetic variation associated with the c.795_805+26[7] polymorphism contributes to 17% and 13% of the variance of FVII:C and FVII:Ag respectively (8548429)" | A quantitative analysis of transcripts indicated a parallel decrease of the IVS7 repeat number and mRNA relative expression (VNTR[6] being considered as a reference). VNTR[7] showed higher values than VNTR[6] (10828024)" | |
| 994 | rs6041 | Point | Intronic | Intron (8) | c.806-20G>A | 45 | 0.1274271 | WT=I1: Var=I2 | Ischemic stroke is associated with the ABO locus: the EuroCLOT study. | |||
| 998 | rs6046 | Point | Missense | Exon (9) | c.1238G>A | p.(Arg413Gln (R353Q)) | 116 | 0.1265056 | R353Q: WT=M1: Var=M2 | In linkage disequilibrium with the c.-401T/c.-325_-324ins10/c.-122C haplotype | Genetic variation associated with the p.(Arg413Gln) polymorphism contributes to 30% and 23% of the variance of FVII:C and FVII:Ag respectively (8548429; 9409261)" | Transient transfection assays with a F7 cDNA containing the base substitution resulting in Gln413 showed a FVII secretion decrease to 74% compared to wild type (9409261)" |