rs11857532

Variant names:

• chr15-78675926-T-G
• rs11857532
• ENST00000560511.5:n.229-20263A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000560511.5(CHRNB4):​n.229-20263A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,016 control chromosomes in the GnomAD database, including 13,962 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 0.42 (13962 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 15 publications found

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

ENSG00000290426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000560511.5	n.229-20263A>C		intron_variant	Intron 2 of 6	3
ENSG00000290426	ENST00000569846.2	n.366+14392T>G		intron_variant	Intron 2 of 5	4
ENSG00000290426	ENST00000846725.1	n.400+14392T>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63883 AN: 151898 Hom.: 13951 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63921 AN: 152016 Hom.: 13962 Cov.: 32 AF XY: 0.411 AC XY: 30509 AN XY: 74298

African (AFR) AF: 0.469 AC: 19444 AN: 41458

American (AMR) AF: 0.317 AC: 4846 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1493 AN: 3468

East Asian (EAS) AF: 0.0817 AC: 422 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 3990 AN: 10564

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 31013 AN: 67940

Other (OTH) AF: 0.409 AC: 862 AN: 2108

Alfa AF: 0.439 Hom.: 9078

Bravo AF: 0.419

Asia WGS AF: 0.176 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.62
PhyloP100		0.084

Splicing

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

Other links and lift over

dbSNP: rs11857532; hg19: chr15-78968268;