rs11072793

Variant names:

• chr15-78714100-G-A
• rs11072793
• ENST00000558216.1:n.144-5995C>T

Variant summary

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

The ENST00000558216.1(CHRNB4):​n.144-5995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,026 control chromosomes in the GnomAD database, including 28,567 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 0.58 (28567 hom., cov: 32)
• Consequence: CHRNB4 ENST00000558216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 20 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1348-5995C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932509.2	n.1304-5995C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932510.3	n.449+1512C>T		intron_variant	Intron 1 of 2
LOC105370913	XR_932511.3	n.257+4268C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.144-5995C>T		intron_variant	Intron 1 of 2	2
CHRNB4	ENST00000560511.5	n.111-5995C>T		intron_variant	Intron 1 of 6	3
ENSG00000290426	ENST00000565476.5	n.317-5205G>A		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88645 AN: 151908 Hom.: 28565 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.583 AC: 88663 AN: 152026 Hom.: 28567 Cov.: 32 AF XY: 0.578 AC XY: 42916 AN XY: 74288

African (AFR) AF: 0.303 AC: 12555 AN: 41430

American (AMR) AF: 0.601 AC: 9188 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2435 AN: 5178

South Asian (SAS) AF: 0.538 AC: 2593 AN: 4818

European-Finnish (FIN) AF: 0.598 AC: 6307 AN: 10552

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51100 AN: 67988

Other (OTH) AF: 0.595 AC: 1255 AN: 2110

Alfa AF: 0.695 Hom.: 135868

Bravo AF: 0.572

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.19
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs11072793; hg19: chr15-79006442;