rs376604413
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000747.3(CHRNB1):āc.578A>Gā(p.Gln193Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000747.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNB1 | NM_000747.3 | c.578A>G | p.Gln193Arg | missense_variant | 6/11 | ENST00000306071.7 | NP_000738.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.578A>G | p.Gln193Arg | missense_variant | 6/11 | 1 | NM_000747.3 | ENSP00000304290.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251482Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727242
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 26, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNB1 protein function. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 193 of the CHRNB1 protein (p.Gln193Arg). This variant is present in population databases (rs376604413, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CHRNB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 570481). 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