rs55855125
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_000744.7(CHRNA4):c.1448G>A(p.Arg483Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000195 in 1,562,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R483W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1448G>A | p.Arg483Gln | missense_variant | 5/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.920G>A | p.Arg307Gln | missense_variant | 5/6 | ||
CHRNA4 | NR_046317.2 | n.1657G>A | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1448G>A | p.Arg483Gln | missense_variant | 5/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152192Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000113 AC: 20AN: 176754Hom.: 0 AF XY: 0.000104 AC XY: 10AN XY: 95940
GnomAD4 exome AF: 0.000200 AC: 282AN: 1410694Hom.: 0 Cov.: 83 AF XY: 0.000188 AC XY: 131AN XY: 696276
GnomAD4 genome AF: 0.000145 AC: 22AN: 152192Hom.: 0 Cov.: 34 AF XY: 0.0000941 AC XY: 7AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2016 | The R483Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R483Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Autosomal dominant nocturnal frontal lobe epilepsy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Center for Precision Medicine, Vanderbilt University Medical Center | Mar 16, 2018 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 1;C1861063:Tobacco addiction, susceptibility to Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 20, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at