rs796052318
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_000744.7(CHRNA4):āc.1316A>Cā(p.Lys439Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,529,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1316A>C | p.Lys439Thr | missense_variant | 5/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.788A>C | p.Lys263Thr | missense_variant | 5/6 | ||
CHRNA4 | NR_046317.2 | n.1525A>C | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1316A>C | p.Lys439Thr | missense_variant | 5/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152082Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000726 AC: 10AN: 1377912Hom.: 0 Cov.: 83 AF XY: 0.00000444 AC XY: 3AN XY: 675374
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 14, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; 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) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 01, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 24, 2017 | The p.K439T variant (also known as c.1316A>C), located in coding exon 5 of the CHRNA4 gene, results from an A to C substitution at nucleotide position 1316. The lysine at codon 439 is replaced by threonine, an amino acid with similar properties. 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 alteration remains unclear. - |
Autosomal dominant nocturnal frontal lobe epilepsy 1;C1861063:Tobacco addiction, susceptibility to Uncertain:1
Uncertain significance, no assertion criteria provided | research | Division of Human Genetics, Children's Hospital of Philadelphia | Apr 14, 2016 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at