rs56142348
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000744.7(CHRNA4):c.1203G>C(p.Leu401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,603,400 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign 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. L401L) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1203G>C | p.Leu401= | synonymous_variant | 5/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.675G>C | p.Leu225= | synonymous_variant | 5/6 | ||
CHRNA4 | NR_046317.2 | n.1412G>C | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1203G>C | p.Leu401= | synonymous_variant | 5/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000605 AC: 92AN: 152184Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000901 AC: 207AN: 229768Hom.: 3 AF XY: 0.000797 AC XY: 100AN XY: 125426
GnomAD4 exome AF: 0.000445 AC: 646AN: 1451216Hom.: 5 Cov.: 98 AF XY: 0.000449 AC XY: 324AN XY: 720922
GnomAD4 genome ? AF: 0.000605 AC: 92AN: 152184Hom.: 2 Cov.: 32 AF XY: 0.000552 AC XY: 41AN XY: 74338
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 03, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 27, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 09, 2015 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
CHRNA4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at