Variant 1-154572175-G-T 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 NM_000748.3(CHRNB2):c.1338+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,536,424 control chromosomes in the GnomAD database, including 6,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 563 hom., cov: 32)

Exomes 𝑓: 0.087 ( 5534 hom. )

Consequence

CHRNB2
NM_000748.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.531

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]

CHRNB2 links:

CHRNB2 (HGNC:):

CHRNB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-154572175-G-T is Benign according to our data. Variant chr1-154572175-G-T is described in ClinVar as [Benign]. Clinvar id is 158331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154572175-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHRNB2	NM_000748.3 linkuse as main transcript	c.1338+14G>T	intron_variant	ENST00000368476.4	NP_000739.1	P17787Q5SXY3
CHRNB2	XM_017000180.3 linkuse as main transcript	c.828+14G>T	intron_variant		XP_016855669.1
CHRNB2	XR_001736952.3 linkuse as main transcript	n.1605+14G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CHRNB2	ENST00000368476.4 linkuse as main transcript	c.1338+14G>T	intron_variant	1	NM_000748.3	ENSP00000357461.3	P17787
CHRNB2	ENST00000637900.1 linkuse as main transcript	c.1344+14G>T	intron_variant	5		ENSP00000490474.1	A0A1B0GVD7
CHRNB2	ENST00000636034.1 linkuse as main transcript	n.1338+14G>T	intron_variant	5		ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12285

AN:

152122

Hom.:

568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0984

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0837

Gnomad OTH

AF:

0.0941

GnomAD3 exomes

AF:

0.0989

AC:

13032

AN:

131748

Hom.:

734

AF XY:

0.101

AC XY:

7300

AN XY:

71934

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.0932

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0542

Gnomad NFE exome

AF:

0.0853

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0865

AC:

119776

AN:

1384182

Hom.:

5534

Cov.:

AF XY:

0.0881

AC XY:

60206

AN XY:

683138

show subpopulations

Gnomad4 AFR exome

AF:

0.0564

Gnomad4 AMR exome

AF:

0.0939

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.0518

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0923

GnomAD4 genome

AF:

0.0807

AC:

12283

AN:

152242

Hom.:

563

Cov.:

AF XY:

0.0806

AC XY:

6002

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0563

Gnomad4 AMR

AF:

0.0984

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0555

Gnomad4 NFE

AF:

0.0837

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.0835

Hom.:

103

Bravo

AF:

0.0815

Asia WGS

AF:

0.143

AC:

499

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nocturnal frontal lobe epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.73

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

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