rs373676452
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000748.3(CHRNB2):c.788G>A(p.Gly263Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,092 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 (★).
Frequency
Consequence
NM_000748.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.788G>A | p.Gly263Asp | missense_variant | Exon 5 of 6 | ENST00000368476.4 | NP_000739.1 | |
CHRNB2 | XM_017000180.3 | c.278G>A | p.Gly93Asp | missense_variant | Exon 2 of 3 | XP_016855669.1 | ||
CHRNB2 | XR_001736952.3 | n.1055G>A | non_coding_transcript_exon_variant | Exon 5 of 7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.788G>A | p.Gly263Asp | missense_variant | Exon 5 of 6 | 1 | NM_000748.3 | ENSP00000357461.3 | ||
CHRNB2 | ENST00000637900.1 | c.794G>A | p.Gly265Asp | missense_variant | Exon 5 of 6 | 5 | ENSP00000490474.1 | |||
CHRNB2 | ENST00000636034.1 | n.788G>A | non_coding_transcript_exon_variant | Exon 5 of 9 | 5 | ENSP00000489703.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
This sequence change replaces glycine with aspartic acid at codon 263 of the CHRNB2 protein (p.Gly263Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs373676452, ExAC 0.001%). This variant has not been reported in the literature in individuals with CHRNB2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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