chr15-78714240-T-C

Variant names:

• chr15-78714240-T-C
• rs11072794
• ENST00000558216.1:n.144-6135A>G

Variant summary

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

The ENST00000558216.1(CHRNB4):​n.144-6135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,060 control chromosomes in the GnomAD database, including 28,022 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 0.57 (28022 hom., cov: 32)
• Consequence: CHRNB4 ENST00000558216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 22 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 = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1348-6135A>G		intron_variant	Intron 1 of 2
LOC105370913	XR_932509.2	n.1304-6135A>G		intron_variant	Intron 1 of 2
LOC105370913	XR_932510.3	n.449+1372A>G		intron_variant	Intron 1 of 2
LOC105370913	XR_932511.3	n.257+4128A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.144-6135A>G		intron_variant	Intron 1 of 2	2
CHRNB4	ENST00000560511.5	n.110+5937A>G		intron_variant	Intron 1 of 6	3
ENSG00000290426	ENST00000565476.5	n.317-5065T>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86640 AN: 151942 Hom.: 28021 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.570 AC: 86651 AN: 152060 Hom.: 28022 Cov.: 32 AF XY: 0.565 AC XY: 41980 AN XY: 74318

African (AFR) AF: 0.255 AC: 10563 AN: 41464

American (AMR) AF: 0.597 AC: 9119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2327 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2509 AN: 5174

South Asian (SAS) AF: 0.538 AC: 2590 AN: 4812

European-Finnish (FIN) AF: 0.597 AC: 6315 AN: 10572

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51082 AN: 67986

Other (OTH) AF: 0.590 AC: 1243 AN: 2108

Alfa AF: 0.684 Hom.: 48712

Bravo AF: 0.557

Asia WGS AF: 0.456 AC: 1591 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	6.0
DANN	Benign	0.66
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs11072794; hg19: chr15-79006582;