rs72558026
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_199037.5(SCN1B):c.560G>A(p.Arg187His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,610,784 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R187L) has been classified as Likely benign.
Frequency
Consequence
NM_199037.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.448+112G>A | intron_variant | ENST00000262631.11 | NP_001028.1 | |||
SCN1B | NM_199037.5 | c.560G>A | p.Arg187His | missense_variant | 3/3 | NP_950238.1 | ||
SCN1B | NM_001321605.2 | c.349+112G>A | intron_variant | NP_001308534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.448+112G>A | intron_variant | 1 | NM_001037.5 | ENSP00000262631.3 |
Frequencies
GnomAD3 genomes AF: 0.000697 AC: 106AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00149 AC: 364AN: 244964Hom.: 5 AF XY: 0.00142 AC XY: 189AN XY: 133376
GnomAD4 exome AF: 0.000380 AC: 554AN: 1458646Hom.: 9 Cov.: 33 AF XY: 0.000375 AC XY: 272AN XY: 725324
GnomAD4 genome AF: 0.000684 AC: 104AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.000834 AC XY: 62AN XY: 74348
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 09, 2018 | Variant summary: SCN1B c.560G>A (p.Arg187His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 271814 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 137-fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN1B causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. The variant, c.560G>A, has been reported in the literature in individuals affected with idiopathic cardiac arrest and one patient with cardiopulmonary arrest and Brugada-pattern electrocardiogram (Mellor_2017, Nakajima_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Ventricular fibrillation Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Aug 26, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Brugada syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at