rs121434627
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_001037.5(SCN1B):c.259G>A(p.Glu87Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E87Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001037.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.259G>A | p.Glu87Lys | missense_variant | 3/6 | ENST00000262631.11 | |
SCN1B | NM_199037.5 | c.259G>A | p.Glu87Lys | missense_variant | 3/3 | ||
SCN1B | NM_001321605.2 | c.160G>A | p.Glu54Lys | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.259G>A | p.Glu87Lys | missense_variant | 3/6 | 1 | NM_001037.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251356Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727198
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74304
ClinVar
Submissions by phenotype
Brugada syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2020 | This sequence change replaces glutamic acid with lysine at codon 87 of the SCN1B protein (p.Glu87Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121434627, ExAC 0.006%). This variant has not been reported in the literature in individuals with SCN1B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at