rs773706734
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000748.3(CHRNB2):c.201C>T(p.Leu67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,978 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
CHRNB2
NM_000748.3 synonymous
NM_000748.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.735
Genes affected
CHRNB2 (HGNC:1962): (cholinergic receptor nicotinic beta 2 subunit) Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 1-154569598-C-T is Benign according to our data. Variant chr1-154569598-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 477013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.735 with no splicing effect.
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.201C>T | p.Leu67= | synonymous_variant | 2/6 | ENST00000368476.4 | |
CHRNB2 | XR_001736952.3 | n.468C>T | non_coding_transcript_exon_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.201C>T | p.Leu67= | synonymous_variant | 2/6 | 1 | NM_000748.3 | P4 | |
CHRNB2 | ENST00000637900.1 | c.201C>T | p.Leu67= | synonymous_variant | 2/6 | 5 | A1 | ||
CHRNB2 | ENST00000636695.1 | n.71C>T | non_coding_transcript_exon_variant | 1/3 | 5 | ||||
CHRNB2 | ENST00000636034.1 | c.201C>T | p.Leu67= | synonymous_variant, NMD_transcript_variant | 2/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251376Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135866
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461836Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18AN XY: 727222
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74308
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | CHRNB2: BP4, BP7 - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2016 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at