GeneBe

chr1-154568062-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000748.3(CHRNB2):​c.18C>T​(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G6G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CHRNB2
NM_000748.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.132
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 1-154568062-C-T is Benign according to our data. Variant chr1-154568062-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3706321.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.132 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHRNB2NM_000748.3 linkc.18C>T p.Gly6Gly synonymous_variant Exon 1 of 6 ENST00000368476.4 NP_000739.1 P17787Q5SXY3
CHRNB2XR_001736952.3 linkn.285C>T non_coding_transcript_exon_variant Exon 1 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRNB2ENST00000368476.4 linkc.18C>T p.Gly6Gly synonymous_variant Exon 1 of 6 1 NM_000748.3 ENSP00000357461.3 P17787

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1448854
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
719796
African (AFR)
AF:
0.00
AC:
0
AN:
33256
American (AMR)
AF:
0.00
AC:
0
AN:
43624
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25854
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39082
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84088
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50008
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5716
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1107416
Other (OTH)
AF:
0.00
AC:
0
AN:
59810
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Oct 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
13
DANN
Benign
0.94
PhyloP100
0.13
PromoterAI
-0.056
Neutral
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1571019072; hg19: chr1-154540538; API