rs786205833
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001037.5(SCN1B):āc.23T>Cā(p.Val8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,007,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V8L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001037.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.23T>C | p.Val8Ala | missense_variant | 1/6 | ENST00000262631.11 | |
SCN1B | NM_199037.5 | c.23T>C | p.Val8Ala | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.23T>C | p.Val8Ala | missense_variant | 1/6 | 1 | NM_001037.5 | P1 | |
SCN1B | ENST00000415950.5 | c.23T>C | p.Val8Ala | missense_variant | 1/3 | 1 | |||
SCN1B | ENST00000638536.1 | c.23T>C | p.Val8Ala | missense_variant | 1/5 | 1 | P1 | ||
SCN1B | ENST00000595652.5 | c.23T>C | p.Val8Ala | missense_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000269 AC: 4AN: 148506Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000105 AC: 9AN: 858512Hom.: 0 Cov.: 12 AF XY: 0.0000121 AC XY: 5AN XY: 413890
GnomAD4 genome ? AF: 0.0000269 AC: 4AN: 148506Hom.: 0 Cov.: 31 AF XY: 0.0000276 AC XY: 2AN XY: 72384
ClinVar
Submissions by phenotype
Brugada syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2023 | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 190868). This missense change has been observed in individual(s) with SCN1B-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 8 of the SCN1B protein (p.Val8Ala). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2022 | The p.V8A variant (also known as c.23T>C), located in coding exon 1 of the SCN1B gene, results from a T to C substitution at nucleotide position 23. The valine at codon 8 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at