rs35478147
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001037.5(SCN1B):c.522C>A(p.Leu174Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,614,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001037.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.522C>A | p.Leu174Leu | synonymous_variant | Exon 4 of 6 | ENST00000262631.11 | NP_001028.1 | |
SCN1B | NM_001321605.2 | c.423C>A | p.Leu141Leu | synonymous_variant | Exon 4 of 6 | NP_001308534.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251478Hom.: 1 AF XY: 0.000118 AC XY: 16AN XY: 135918
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461848Hom.: 3 Cov.: 31 AF XY: 0.0000811 AC XY: 59AN XY: 727232
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74314
ClinVar
Submissions by phenotype
not specified Benign:2
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Cardiovascular phenotype Uncertain:1
The c.522C>A variant (also known as p.L174L), located in coding exon 4 of the SCN1B gene, results from a C to A substitution at nucleotide position 522. This nucleotide substitution does not change the leucine at codon 174. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. According to data from gnomAD, the frequency for this variant is above the maximum credible frequency for a cardiac disease-causing variant and an autosomal dominant epilepsy disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). Based on the supporting evidence, this variant is unlikely to be causative of SCN1B-related arrhythmia or autosomal dominant SCN1B-related epilepsy; however, its contribution to the development of autosomal recessive SCN1B-related developmental and epileptic encephalopathy is uncertain. -
Brugada syndrome 5 Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at