Table 1. Genetic variants detected by Sanger sequencing of the ISL1 gene.
| No. | Intron/exon | Position Chr 5 (hg19) | Variation | SNP | Regulome scorea | CADD (M-CAP) | Alternate allele frequency (%) |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Our case | 1kG ALLb | 1kG EURb | ExAC NFE | gnomAD NFE | SweGen | |||||||
| 1 | 5ʹ UTR | 50679014 | c.-492A>G | rs3762977 | 4 | 6.4 | 16.1 | 14.1 | 12.3 | — | 15.6 | 11.6 |
| 2 | 5ʹ UTR | 50679024 | c.-482G>C | rs71618117 | 4 | 4.7 | 0.4 | 0.1 | 0.3 | — | 0.4 | 1.5 |
| 3 c | 5ʹ UTR | 50679204 | c.-302A>G | rs36216897 | 4 | 13.7 | 2.4 | 0.4 | 1.3 | — | 1.9 | 1.3 |
| 4 c | 5ʹ UTR | 50679266 | c.-240G>A | rs116222082 | 4 | 13.6 | 1.6 | 0.5 | 1.8 | — | 1.2 | 1.5 |
| 5 c | 5ʹ UTR | 50679292 | c.-214C>A | rs532316340 | 4 | 12.8 | 0.4 | — | 0.1 | — | 0.3 | — |
| 6 | 5ʹ UTR | 50679459 | c.-47A>G | rs3917084 | 4 | 12.1 | 3.1 | 1.1 | 3.6 | 3.7 | 2.4 | 4.1 |
| 7 | Intron 1 | 50679550 | c.28+17C>T | rs150104955 | 4 | 11.8 | 3.2 | 1.0 | 3.1 | 3.3 | 3.5 | 3.9 |
| 8 | Intron 1 | 50680233 | c.29-142G>A | rs4865658 | 5 | 3.9 | 52 | 40.2 | 35.8 | — | 38.0 | 39.4 |
| 9 | Intron 1 | 50680249 | c.29-126A>G | rs4151674 | 5 | 0.001 | 3.2 | 1.9 | 5.1 | — | 5.4 | 5.8 |
| 10 | Intron 1 | 50680253 | c.29-122G>A | none | 2b | Unknown | 0.8 | — | — | — | — | — |
| 11 | Intron 1 | 50680273 | c.29-102A>G | rs4151675 | 3a | 0.003 | 0.8 | 0.02 | — | — | — | 0.1 |
| 12 c | Exon 2 | 50680483 | c.137C>G;p.(Ala46Gly) | None | 3a | 19.4 (0.52) | 0.4 | — | — | — | — | — |
| 13 | Intron 3 | 50683655 | c.478+72T>C | rs2288468 | 4 | 7.6 | 45.7 | 40.1 | 35.9 | — | 37.8 | 39.6 |
| 14 | Intron 3 | 50683807 | c.478+224C>A | rs73095545 | 4 | 6.1 | 0.4 | 2.3 | — | — | 0.007 | 0.05 |
| 15 c, d | Intron 3 | 50685476 | c.479-4G>A | rs2303750 | 4 | 13.0 | 0.4 | 1.6 | 0.3 | 0.2 | 0.9 | 0.1 |
| 16b | Exon 4 | 50685505 | c.504A>G;p.(Pro168=) | rs2303751 | 2b | 10.3 | 52.9 | 37.7 | 36.0 | 39.2 | 36.9 | 39.6 |
| 17b | Intron 4 | 50685819 | c.765+53T>C | None | 4 | 3.0 | 0.4 | — | — | — | — | — |
| 18b | Intron 4 | 50686062 | c.765+296G>A | rs113256352 | 4 | 3.0 | 0.4 | 1.0 | — | — | 1.1 | — |
| 19 c | Intron 4 | 50687007 | c.766-101A>G | rs189872668 | 2b | 20.0 | 2.0 | 0.2 | 0.4 | 0.8 | — | 1.5 |
| 20 | Intron 4 | 50687087 | c.766-21G>T | rs182071569 | 2b | 7.0 | 0.4 | 0.1 | 0.2 | 0.2 | 0.1 | 0.3 |
| 21 c | Exon 5 | 50687227 | c.885C>T;(p.Ser295=) | rs41268419 | 4 | 9.2 | 0.4 | 0.1 | 0.3 | 0.4 | 0.2 | 0.5 |
2b, transcription factor (TF) binding+any motif+DNase footprint+DNase peak; 3a, TF binding+any motif+DNase peak; 4, TF binding+DNase peak; and 5, TF binding or DNase peak; —, no frequency information available.
Abbreviations: CADD, Combined Annotation Dependent Depletion; ExAC, Exome Aggregation Consortium; gnomAD, Genome Aggregation Database; NFE, Non-Finnish European population; SNP, single-nucleotide polymorphism; M-CAP, Mendelian Clinically Applicable Pathogenicity.
a
Regulome scoring refers to all the DNA features and regulatory regions that have been identified to contain the variant coordinates.
b
Data from 1000 Genomes.
c
Variant predicted as disease causing by MutationTaster, marked as bold text.
d
n=122.