rs779199533
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_000748.3(CHRNB2):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,434 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R106W) has been classified as Likely benign.
Frequency
Consequence
NM_000748.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.317G>A | p.Arg106Gln | missense_variant | 4/6 | ENST00000368476.4 | |
CHRNB2 | XM_017000180.3 | c.-58G>A | 5_prime_UTR_variant | 1/3 | |||
CHRNB2 | XR_001736952.3 | n.584G>A | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.317G>A | p.Arg106Gln | missense_variant | 4/6 | 1 | NM_000748.3 | P4 | |
CHRNB2 | ENST00000637900.1 | c.323G>A | p.Arg108Gln | missense_variant | 4/6 | 5 | A1 | ||
CHRNB2 | ENST00000636034.1 | c.317G>A | p.Arg106Gln | missense_variant, NMD_transcript_variant | 4/9 | 5 | |||
CHRNB2 | ENST00000636695.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248876Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134382
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460408Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726336
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74240
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 106 of the CHRNB2 protein (p.Arg106Gln). This variant is present in population databases (rs779199533, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHRNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205065). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNB2 protein function with a negative predictive value of 80%. 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. - |
Autosomal dominant nocturnal frontal lobe epilepsy 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at