15-78672156-A-G

Variant names:

• chr15-78672156-A-G
• rs8032156
• ENST00000560511.5:n.229-16493T>C

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.229-16493T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,106 control chromosomes in the GnomAD database, including 43,513 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 0.75 (43513 hom., cov: 33)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000560511.5	TSL:3	n.229-16493T>C		intron	N/A
	ENSG00000290426	ENST00000569846.2	TSL:4	n.366+10622A>G		intron	N/A
	ENSG00000290426	ENST00000846725.1		n.400+10622A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114179 AN: 151988 Hom.: 43493 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.751 AC: 114236 AN: 152106 Hom.: 43513 Cov.: 33 AF XY: 0.741 AC XY: 55091 AN XY: 74356

African (AFR) AF: 0.716 AC: 29727 AN: 41506

American (AMR) AF: 0.617 AC: 9428 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2814 AN: 3472

East Asian (EAS) AF: 0.583 AC: 3003 AN: 5154

South Asian (SAS) AF: 0.614 AC: 2960 AN: 4822

European-Finnish (FIN) AF: 0.707 AC: 7480 AN: 10580

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56199 AN: 67974

Other (OTH) AF: 0.744 AC: 1572 AN: 2112

Alfa AF: 0.799 Hom.: 145474

Bravo AF: 0.746

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.54
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs8032156; hg19: chr15-78964498;