Variant rs2072658 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000666466.2(ENSG00000286391):n.1C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 378,710 control chromosomes in the GnomAD database, including 522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 144 hom., cov: 32)

Exomes 𝑓: 0.026 ( 378 hom. )

Consequence

ENSG00000286391
ENST00000666466.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

ENSG00000286391 (HGNC:):

ENSG00000286391 links:

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]

CHRNB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-154567749-G-A is Benign according to our data. Variant chr1-154567749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 673243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHRNB2	NM_000748.3 link	c.-296G>A	upstream_gene_variant	ENST00000368476.4	NP_000739.1	P17787Q5SXY3
CHRNB2	XR_001736952.3 link	n.-29G>A	upstream_gene_variant
LOC107985206	XR_001738237.2 link	n.-32C>T	upstream_gene_variant
LOC107985206	XR_001738238.3 link	n.-32C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4 link	c.-296G>A		upstream_gene_variant		1	NM_000748.3	ENSP00000357461.3		P17787

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2957

AN:

151630

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.00190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0140

GnomAD4 exome

AF:

0.0257

AC:

5839

AN:

226970

Hom.:

378

Cov.:

AF XY:

0.0243

AC XY:

2820

AN XY:

115866

show subpopulations

Gnomad4 AFR exome

AF:

0.00238

Gnomad4 AMR exome

AF:

0.0859

Gnomad4 ASJ exome

AF:

0.000921

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.00416

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0196

AC:

2967

AN:

151740

Hom.:

144

Cov.:

AF XY:

0.0208

AC XY:

1545

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.00388

Gnomad4 AMR

AF:

0.0691

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.00706

Gnomad4 FIN

AF:

0.00190

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.0208

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0520

AC:

181

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal dominant nocturnal frontal lobe epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.81

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over