rs149083639
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000080.4(CHRNE):c.1345C>T(p.Arg449Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,582,816 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. R449S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000080.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.1345C>T | p.Arg449Cys | missense_variant | 12/12 | ENST00000649488.2 | |
CHRNE | XM_017024115.2 | c.1309C>T | p.Arg437Cys | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.1345C>T | p.Arg449Cys | missense_variant | 12/12 | NM_000080.4 | P1 | ||
CHRNE | ENST00000649830.1 | c.521C>T | p.Ala174Val | missense_variant | 11/11 | ||||
CHRNE | ENST00000572438.1 | n.1031C>T | non_coding_transcript_exon_variant | 7/7 | 5 | ||||
CHRNE | ENST00000652550.1 | n.1071C>T | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000410 AC: 8AN: 195048Hom.: 0 AF XY: 0.0000286 AC XY: 3AN XY: 104736
GnomAD4 exome AF: 0.00000699 AC: 10AN: 1430514Hom.: 1 Cov.: 34 AF XY: 0.00000988 AC XY: 7AN XY: 708732
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74478
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 449 of the CHRNE protein (p.Arg449Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 534258). 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 CHRNE protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 12, 2023 | - - |
Congenital myasthenic syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at