rs11072791

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000290426 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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
ENSG00000290426	ENST00000565476.5	n.197+762C>A		intron_variant	Intron 1 of 4	4

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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.314

Alfa AF: 0.362 Hom.: 1902

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11072791; hg19: chr15-78997076;