dbSNP rs12900519: CHRNB4:n.-708-95G>A (chr15-78656785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000559849.5(CHRNB4):n.-708-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,156 control chromosomes in the GnomAD database, including 59,172 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 59172 hom., cov: 31)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CHRNB4
ENST00000559849.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

lung cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CHRNB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB4	XM_011521186.3 link	c.-229-1122G>A		intron_variant	Intron 2 of 9		XP_011519488.1
CHRNB4	XM_011521187.3 link	c.-135-1122G>A		intron_variant	Intron 2 of 8		XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000559849.5 link	n.-708-95G>A		intron_variant	Intron 3 of 11	1		ENSP00000457404.1		H3BU02
CHRNB4	ENST00000560511.5 link	n.229-1122G>A		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133809

AN:

152032

Hom.:

59146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.811

Gnomad AMI

AF:

0.942

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.925

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.929

Gnomad OTH

AF:

0.886

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.880

AC:

133895

AN:

152152

Hom.:

59172

Cov.:

AF XY:

0.877

AC XY:

65205

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.811

AC:

33648

AN:

41472

American (AMR)

AF:

0.870

AC:

13301

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

3181

AN:

3472

East Asian (EAS)

AF:

0.772

AC:

3992

AN:

5168

South Asian (SAS)

AF:

0.925

AC:

4464

AN:

4828

European-Finnish (FIN)

AF:

0.862

AC:

9122

AN:

10586

Middle Eastern (MID)

AF:

0.935

AC:

275

AN:

294

European-Non Finnish (NFE)

AF:

0.929

AC:

63185

AN:

68016

Other (OTH)

AF:

0.884

AC:

1868

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

805

1610

2415

3220

4025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.918

Hom.:

115141

Bravo

AF:

0.877

Asia WGS

AF:

0.828

AC:

2882

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.8

(source)

DANN

Benign

0.30

PhyloP100

0.23

Splicing

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

Publications

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rs12900519

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over