chr17-7446929-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000747.3(CHRNB1):c.340G>A(p.Val114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,613,336 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V114V) has been classified as Likely benign.
Frequency
Consequence
NM_000747.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB1 | NM_000747.3 | c.340G>A | p.Val114Met | missense_variant | 4/11 | ENST00000306071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.340G>A | p.Val114Met | missense_variant | 4/11 | 1 | NM_000747.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000249 AC: 62AN: 248858Hom.: 1 AF XY: 0.000274 AC XY: 37AN XY: 135262
GnomAD4 exome AF: 0.000252 AC: 368AN: 1461204Hom.: 1 Cov.: 33 AF XY: 0.000261 AC XY: 190AN XY: 726882
GnomAD4 genome AF: 0.000230 AC: 35AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | CHRNB1: PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 17, 2020 | - - |
Congenital myasthenic syndrome 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 114 of the CHRNB1 protein (p.Val114Met). This variant is present in population databases (rs149433073, gnomAD 0.05%). 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: 575763). 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 with a negative predictive value of 80%. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.340G>A (p.V114M) alteration is located in exon 4 (coding exon 4) of the CHRNB1 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the valine (V) at amino acid position 114 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital myasthenic syndrome 4C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at