rs762374374
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000744.7(CHRNA4):c.1148G>A(p.Arg383His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,610,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R383C) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1148G>A | p.Arg383His | missense_variant | 5/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.620G>A | p.Arg207His | missense_variant | 5/6 | ||
CHRNA4 | NR_046317.2 | n.1357G>A | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1148G>A | p.Arg383His | missense_variant | 5/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000579 AC: 14AN: 241762Hom.: 0 AF XY: 0.0000530 AC XY: 7AN XY: 132090
GnomAD4 exome AF: 0.0000528 AC: 77AN: 1458790Hom.: 0 Cov.: 99 AF XY: 0.0000455 AC XY: 33AN XY: 725602
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74336
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at