Table 5.
Selected rare variants in the cohort of 120 unrelated multiple sclerosis patients.
| Gene | SNP position GRCh37/hg19 | SNP ID | Transcript (exon) | Amino acid change | SIFT/ PolyPhen prediction | Nucleotide change | MAF % in MS patients alleles n = 240 (n alleles) | MAF % 1000 GP (Tuscany) alleles n = 214 | MAF % dbSNP150 | MAF % ExAC European (not Finnish) | MAF % controls GnomAD European (not Finnish) | P-value° (Tuscany) | P-value° (dbSNP150) | P-value°(ExAC) | P-value° (controls GnomAD) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ADAMTS3 | 4:73414590 | – | ENST0000 0286657 (3/22) | Lys37Glu | 0.17/-0.01$ | T > C | 0(0) | – | – | – | – | – | – | – | – |
| ANKRD55 | 5:55407449 | rs77017041 | ENST0000 0341048 (10/12) | Ser376Pro | 0.01/0.767 | A > G | 0(0) | 0.47 | 0.427 | 0.63 | 0.71 | 0.2871 | 0.3103 | 0.2174 | 0.1902 |
| C6orf10 | 6:32261153 | rs16870005 | ENST000 00533191 (26/26) | Ala431Thr | 0.46/0.028 | C > T | 3.75 (9) | 1.4 | 1.250 | 1.43 | 0.85 | 0.0019 | 0.00049 | 0.0025 | 9.89 × 10-07 |
| CD86 | 3:121774281 | rs11575853 | ENST000 00330540 (5′UTR) | –56bp from +1 Met | n.a. | A > G | 3.75 (9) | 2.8 | 1.078 | – | 3.1 | 0.3723 | 6.1 × 10-5 | – | 0.5612 |
| EVI5 | 1:92979432 | rs41286809 | ENST000 00540033 (18/18) | Phe749Phe | – | G > A | 0.83 (2) | 0.47 | 1.116 | 1.55 | 1.61 | 0.4105 | 0.6768 | 0.3688 | 0.3391 |
| GC | 4:72669661 | rs76781122 | ENST0000 0504199 (1/14) | Met1Ile | 0.2/0 Start codon | G > T | 4.58 (11) | 5.61 | 1.611 | 3.35 | 2.77 | 0.4895 | 0.00025 | 0.2883 | 0.0869 |
| IL2RA | 10:6054765 | rs12722600 | ENST000 00379959 (3′UTR) | +70 from 273 stop | n.a. | G > A | 7.92 (19) | 4.21 | 1.777 | – | 0.87 | 0.0042 | 6.0 × 10-13 | – | <1.0 × 10-20 |
| MALT1 | 18:56367823 | rs74847855 | ENST000 00348428 (4/17) | Arg217Gly | 0.69/0 | A > G | 4.58 (11) | 1.9 | 3.734 | 4.28 | 4.20 | 0.0019 | 0.4877 | 0.8164 | 0.7672 |
| MMEL1 | 1:2530169 | rs147248515 | ENST000 00378412 (12/24) | Pro368Thr | 0.14/0.326 | G > T | 0(0) | 0 | 0.022 | 0.028 | 0.037 | – | – | – | – |
| STAT4 | 2:191899319 | – | ENST000 00392320 (18/24) | Gln525Gln | – | A > G | 0∗ (0) | – | – | – | – | – | – | – | – |
| TET2 | 4:106156163 | rs61744960 | ENST000 00540549 (3/11) | Gly355Asp | 0.01/0.282 | G > A | 8.33 (20) | 5.6 | 2.614 | 3.77 | 3.69 | 0.0667 | 2.8 × 10-08 | 0.00021 | 0.00014 |
| TOP3A | 17:18217958 | rs2230153 | ENST000 00542570 (1/19) | Ala45Ala | – | G > A | 1.66 (4) | 0.47 | 1.692 | 0.46 | 0.36 | 0.0067 | 0.9757 | 0.0057 | 0.00073 |
| TRAF3 | 14:103371923 | rs138943371 | ENST000 00347662 (11/11) | Ser478Ser | – | C > T | 1.25 (3) | 0.47 | 0.245 | 0.30 | 0.36 | 0.0773 | 0.00164 | 0.0071 | 0.02133 |
| TYK2 | 19:10472452 | rs12720355 | ENST00 000525621 (13/25) | Ile651Ile | – | C > T | 1.66 (4) | 1.4 | 0.962 | 1.38 | 1.45 | 0.7251 | 0.2634 | 0.7034 | 0.77887 |
| WWOX | 16:78458807 | rs7201683 | ENST000 00566780 (7/9) | Leu216Val | 0.19/0.04 | C > G | 2.08 (5) | 0.47 | 1.989 | 1.23 | 1.11 | 0.00026 | 0.9166 | 0.2304 | 0.150086 |
The SIFT and PolyPhen scores (0.0 to 1.0) have opposite meanings. Prediction of the SIFT score ranges 0.0 to 0.05 deleterious; 0.05 to 1.0 tolerated. Prediction of the PolyPhen score ranges: 0.0 to 0.15, benign; 0.15 to 1.0 possibly damaging; 0.85 to 1.0 damaging. n.a., not applicable. $SIFT/Provean prediction for ADAMTS3 = (0.17) tolerated/(-0.01) neutral. ∗Investigated in 218 alleles. °Bonferroni’s correction p-value set to 0.0042. Significant p-values are in bold.