rs201168195
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BS1_SupportingBS2
The NM_000744.7(CHRNA4):c.1825G>T(p.Val609Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,506 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic 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. V609I) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1825G>T | p.Val609Phe | missense_variant | 6/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.1297G>T | p.Val433Phe | missense_variant | 6/6 | ||
CHRNA4 | NR_046317.2 | n.2034G>T | non_coding_transcript_exon_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1825G>T | p.Val609Phe | missense_variant | 6/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000606 AC: 15AN: 247526Hom.: 1 AF XY: 0.0000967 AC XY: 13AN XY: 134462
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460304Hom.: 2 Cov.: 32 AF XY: 0.0000262 AC XY: 19AN XY: 726492
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2021 | This sequence change replaces valine with phenylalanine at codon 609 of the CHRNA4 protein (p.Val609Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CHRNA4-related conditions. This variant is present in population databases (rs201168195, ExAC 0.04%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at