rs11072791

Variant names:

• chr15-78704734-C-A
• rs11072791
• ENST00000558216.1:n.261+3254G>T

Variant summary

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

The ENST00000558216.1(CHRNB4):​n.261+3254G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,080 control chromosomes in the GnomAD database, including 7,792 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 0.29 (7792 hom., cov: 31)
• Consequence: CHRNB4 ENST00000558216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1465+3254G>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932509.2	n.1421+3254G>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932510.3	n.567+3254G>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932511.3	n.375+3254G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.261+3254G>T		intron_variant	Intron 2 of 2	2
CHRNB4	ENST00000560511.5	n.228+3254G>T		intron_variant	Intron 2 of 6	3
CHRNB4	ENST00000560868.1	n.65+3254G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44250 AN: 151962 Hom.: 7787 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.291 AC: 44264 AN: 152080 Hom.: 7792 Cov.: 31 AF XY: 0.286 AC XY: 21262 AN XY: 74336

African (AFR) AF: 0.108 AC: 4469 AN: 41516

American (AMR) AF: 0.315 AC: 4819 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5182

South Asian (SAS) AF: 0.229 AC: 1105 AN: 4816

European-Finnish (FIN) AF: 0.330 AC: 3490 AN: 10560

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27816 AN: 67942

Other (OTH) AF: 0.314 AC: 664 AN: 2112

Alfa AF: 0.355 Hom.: 1913

Bravo AF: 0.284

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.026

Splicing

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

Other links and lift over

dbSNP: rs11072791; hg19: chr15-78997076;