rs201033437
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_000747.3(CHRNB1):āc.516C>Gā(p.Tyr172Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,614,102 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Y172Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000747.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB1 | NM_000747.3 | c.516C>G | p.Tyr172Ter | stop_gained | 6/11 | ENST00000306071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.516C>G | p.Tyr172Ter | stop_gained | 6/11 | 1 | NM_000747.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251482Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135916
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000646 AC XY: 47AN XY: 727246
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4C Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Pathogenic and reported on 07-12-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Oct 30, 2018 | The CHRNB1 c.516C>G (p.Tyr172Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Control data are unavailable for this variant, which is reported at a frequency of 0.000075 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the limited evidence and potential impact of stop-gained variants, the p.Tyr172Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital myasthenic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Congenital myasthenic syndrome 2A Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 31, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 476151). This variant has not been reported in the literature in individuals affected with CHRNB1-related conditions. This variant is present in population databases (rs201033437, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Tyr172*) in the CHRNB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNB1 are known to be pathogenic (PMID: 10562302). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at