rs76378652
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_000744.7(CHRNA4):c.1108C>T(p.Arg370Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,612,852 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R370Q) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1108C>T | p.Arg370Trp | missense_variant | 5/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.580C>T | p.Arg194Trp | missense_variant | 5/6 | ||
CHRNA4 | NR_046317.2 | n.1317C>T | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1108C>T | p.Arg370Trp | missense_variant | 5/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000749 AC: 114AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000257 AC: 64AN: 248912Hom.: 1 AF XY: 0.000207 AC XY: 28AN XY: 135154
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1460654Hom.: 1 Cov.: 99 AF XY: 0.0000537 AC XY: 39AN XY: 726622
GnomAD4 genome ? AF: 0.000749 AC: 114AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.00104 AC XY: 77AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | CHRNA4: BP4, BS1 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2016 | The p.R370W variant (also known as c.1108C>T), located in coding exon 5 of the CHRNA4 gene, results from a C to T substitution at nucleotide position 1108. The arginine at codon 370 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs76378652. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6,501 samples (13,002 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at