Variant 15-78629260-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000750.5(CHRNB4):c.1045C>T(p.Arg349Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 1,613,202 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 60 hom. )

Consequence

CHRNB4
NM_000750.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

CHRNB4 (HGNC:1964): (cholinergic receptor nicotinic beta 4 subunit) This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

CHRNB4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026435733).

BP6

Variant 15-78629260-G-A is Benign according to our data. Variant chr15-78629260-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645613.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	NM_000750.5 linkuse as main transcript	c.1045C>T	p.Arg349Cys	missense_variant	5/6	ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000261751.8 linkuse as main transcript	c.1045C>T	p.Arg349Cys	missense_variant	5/6	1	NM_000750.5	ENSP00000261751	P1	P30926-1
CHRNB4	ENST00000412074.6 linkuse as main transcript	c.359+1816C>T		intron_variant		1		ENSP00000416386		P30926-2

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

841

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00491

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00953

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00522

AC:

1308

AN:

250696

Hom.:

AF XY:

0.00532

AC XY:

720

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00352

Gnomad NFE exome

AF:

0.00854

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00717

AC:

10482

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

5089

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00391

Gnomad4 NFE exome

AF:

0.00850

Gnomad4 OTH exome

AF:

0.00596

GnomAD4 genome

AF:

0.00553

AC:

841

AN:

152206

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

418

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00491

Gnomad4 NFE

AF:

0.00953

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00716

Hom.:

Bravo

AF:

0.00503

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00550

AC:

668

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00664

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CHRNB4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.75

Eigen

Pathogenic

0.79

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.026

MetaSVM

Pathogenic

0.83

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.6

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.76

MVP

0.93

MPC

1.2

ClinPred

0.095

GERP RS

4.2

Varity_R

0.67

gMVP

0.79

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