15-78671652-A-G

Variant names:

• chr15-78671652-A-G
• rs922691
• ENST00000560511.5:n.229-15989T>C

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.229-15989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,186 control chromosomes in the GnomAD database, including 6,960 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 0.30 (6960 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 9 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560511.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000560511.5	TSL:3	n.229-15989T>C		intron	N/A
	ENSG00000290426	ENST00000569846.2	TSL:4	n.366+10118A>G		intron	N/A
	ENSG00000290426	ENST00000846725.1		n.400+10118A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45592 AN: 152068 Hom.: 6960 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.300 AC: 45612 AN: 152186 Hom.: 6960 Cov.: 32 AF XY: 0.295 AC XY: 21962 AN XY: 74408

African (AFR) AF: 0.263 AC: 10908 AN: 41516

American (AMR) AF: 0.227 AC: 3473 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3470

East Asian (EAS) AF: 0.104 AC: 541 AN: 5188

South Asian (SAS) AF: 0.285 AC: 1377 AN: 4824

European-Finnish (FIN) AF: 0.293 AC: 3107 AN: 10606

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23891 AN: 67974

Other (OTH) AF: 0.297 AC: 626 AN: 2110

Alfa AF: 0.332 Hom.: 27673

Bravo AF: 0.291

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs922691; hg19: chr15-78963994;