15-78628735-C-G

Variant names:

• chr15-78628735-C-G
• rs7178270
• NM_000750.5:c.1338+232G>C

Variant summary

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

The NM_000750.5(CHRNB4):​c.1338+232G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,030 control chromosomes in the GnomAD database, including 10,582 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 0.37 (10582 hom., cov: 32)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 25 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

ENSG00000259555 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB4	NM_000750.5	c.1338+232G>C		intron_variant	Intron 5 of 5	ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000261751.8	c.1338+232G>C		intron_variant	Intron 5 of 5	1	NM_000750.5	ENSP00000261751.3
CHRNB4	ENST00000412074.6	c.359+2341G>C		intron_variant	Intron 4 of 4	1		ENSP00000416386.2
ENSG00000259555	ENST00000821537.1	n.312+1170C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56129 AN: 151912 Hom.: 10584 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.369 AC: 56132 AN: 152030 Hom.: 10582 Cov.: 32 AF XY: 0.366 AC XY: 27189 AN XY: 74326

African (AFR) AF: 0.367 AC: 15200 AN: 41446

American (AMR) AF: 0.259 AC: 3960 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1313 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1962 AN: 5178

South Asian (SAS) AF: 0.320 AC: 1546 AN: 4824

European-Finnish (FIN) AF: 0.353 AC: 3735 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27261 AN: 67944

Other (OTH) AF: 0.338 AC: 716 AN: 2116

Alfa AF: 0.248 Hom.: 588

Bravo AF: 0.362

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7178270; hg19: chr15-78921077; COSMIC: COSV107237359; COSMIC: COSV107237359;