Variant rs1948 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000412074.6(CHRNB4):c.594T>C(p.Ala198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,609,104 control chromosomes in the GnomAD database, including 361,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37855 hom., cov: 33)

Exomes 𝑓: 0.66 ( 323365 hom. )

Consequence

CHRNB4
ENST00000412074.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.921

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-78625057-A-G is Benign according to our data. Variant chr15-78625057-A-G is described in ClinVar as [Benign]. Clinvar id is 1289303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.921 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	NM_000750.5 linkuse as main transcript	c.*76T>C		3_prime_UTR_variant	6/6	ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000412074.6 linkuse as main transcript	c.594T>C	p.Ala198=	synonymous_variant	5/5	1		ENSP00000416386		P30926-2
CHRNB4	ENST00000261751.8 linkuse as main transcript	c.*76T>C		3_prime_UTR_variant	6/6	1	NM_000750.5	ENSP00000261751	P1	P30926-1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106744

AN:

151950

Hom.:

37800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.706

GnomAD3 exomes

AF:

0.694

AC:

169878

AN:

244840

Hom.:

59992

AF XY:

0.689

AC XY:

91630

AN XY:

132966

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.705

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.664

AC:

967529

AN:

1457036

Hom.:

323365

Cov.:

AF XY:

0.664

AC XY:

481318

AN XY:

724976

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.851

Gnomad4 ASJ exome

AF:

0.675

Gnomad4 EAS exome

AF:

0.558

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.669

Gnomad4 NFE exome

AF:

0.653

Gnomad4 OTH exome

AF:

0.665

GnomAD4 genome

AF:

0.703

AC:

106854

AN:

152068

Hom.:

37855

Cov.:

AF XY:

0.703

AC XY:

52240

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.786

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.529

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.711

Alfa

AF:

0.669

Hom.:

44810

Bravo

AF:

0.714

Asia WGS

AF:

0.654

AC:

2278

AN:

3478

EpiCase

AF:

0.675

EpiControl

AF:

0.669

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2020	This variant is associated with the following publications: (PMID: 23691088) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.98

DANN

Benign

0.46

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