rs112585933
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000748.3(CHRNB2):c.1235G>A(p.Gly412Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,534,646 control chromosomes in the GnomAD database, including 4 homozygotes. 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. G412S) has been classified as Likely benign.
Frequency
Consequence
NM_000748.3 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 |
---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.1235G>A | p.Gly412Asp | missense_variant | 5/6 | ENST00000368476.4 | |
CHRNB2 | XM_017000180.3 | c.725G>A | p.Gly242Asp | missense_variant | 2/3 | ||
CHRNB2 | XR_001736952.3 | n.1502G>A | non_coding_transcript_exon_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.1235G>A | p.Gly412Asp | missense_variant | 5/6 | 1 | NM_000748.3 | P4 | |
CHRNB2 | ENST00000637900.1 | c.1241G>A | p.Gly414Asp | missense_variant | 5/6 | 5 | A1 | ||
CHRNB2 | ENST00000636034.1 | c.1235G>A | p.Gly412Asp | missense_variant, NMD_transcript_variant | 5/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00124 AC: 188AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00125 AC: 161AN: 128840Hom.: 0 AF XY: 0.00105 AC XY: 74AN XY: 70570
GnomAD4 exome AF: 0.00207 AC: 2858AN: 1382320Hom.: 4 Cov.: 33 AF XY: 0.00195 AC XY: 1332AN XY: 682068
GnomAD4 genome ? AF: 0.00123 AC: 188AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.00110 AC XY: 82AN XY: 74478
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Oct 19, 2017 | BP4, BP6; This alteration is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 16, 2017 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | CHRNB2: PP2, BS1 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 23, 2019 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Sep 28, 2022 | This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.2% (141/68030) (https://gnomad.broadinstitute.org/variant/1-154572058-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:205060). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
CHRNB2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at