chr19-35039667-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001037.5(SCN1B):c.623A>T(p.Lys208Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. K208Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001037.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.623A>T | p.Lys208Ile | missense_variant | 5/6 | ENST00000262631.11 | |
SCN1B | NM_001321605.2 | c.524A>T | p.Lys175Ile | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.623A>T | p.Lys208Ile | missense_variant | 5/6 | 1 | NM_001037.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727242
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Brugada syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2023 | This variant is present in population databases (rs780958012, gnomAD 0.006%). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 470174). This missense change has been observed in individual(s) with febrile seizures (PMID: 19522081). This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 208 of the SCN1B protein (p.Lys208Ile). The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.5, and corresponds to NM_199037.3:c.*5569A>T in the primary transcript. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2020 | The p.K208I variant (also known as c.623A>T), located in coding exon 5 of the SCN1B gene, results from an A to T substitution at nucleotide position 623. The lysine at codon 208 is replaced by isoleucine, an amino acid with dissimilar properties. This variant has been detected in an individual with febrile convulsions (Orrico A et al. Clin. Genet., 2009 Jun;75:579-81). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
SCN1B-related disorder Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at