chr8-27463370-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_000742.4(CHRNA2):c.1073G>T(p.Ser358Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000452 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000742.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000798 AC: 20AN: 250536Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135468
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461764Hom.: 0 Cov.: 33 AF XY: 0.0000605 AC XY: 44AN XY: 727160
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74440
ClinVar
Submissions by phenotype
not provided Uncertain:1
p.Ser358Ile (AGC>ATC): c.1073 G>T in exon 6 of the CHRNA2 gene (NM_000742.3). The S358I missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution, which is is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this amino acid substitution occurs at a position that is not highly conserved across species and does not occur within the transmembrane region of the protein, where the vast majority of pathogenic missense mutations have been identified in association with epilepsy (Steinlein et al., 2010). In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. The variant is found in INFANT-EPI panel(s). -
Autosomal dominant nocturnal frontal lobe epilepsy 4 Uncertain:1
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Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at