15-78688659-T-C

Variant names:

• chr15-78688659-T-C
• rs2869550
• ENST00000560511.5:n.228+19329A>G

Variant summary

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

The ENST00000560868.1(CHRNB4):​n.66-1260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,184 control chromosomes in the GnomAD database, including 756 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 0.038 (756 hom., cov: 31)
• Consequence: CHRNB4 ENST00000560868.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 3 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560868.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000560511.5	TSL:3	n.228+19329A>G		intron	N/A
	CHRNB4	ENST00000560868.1	TSL:2	n.66-1260A>G		intron	N/A
	ENSG00000290426	ENST00000569846.2	TSL:4	n.367-4023T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5719 AN: 152066 Hom.: 751 Cov.: 31

Gnomad AFR AF: 0.00983

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.00755

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0377 AC: 5737 AN: 152184 Hom.: 756 Cov.: 31 AF XY: 0.0427 AC XY: 3178 AN XY: 74398

African (AFR) AF: 0.00992 AC: 412 AN: 41532

American (AMR) AF: 0.189 AC: 2888 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1920 AN: 5156

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4812

European-Finnish (FIN) AF: 0.00755 AC: 80 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00228 AC: 155 AN: 68022

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0184 Hom.: 362

Bravo AF: 0.0541

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.8
DANN	Benign	0.46
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs2869550; hg19: chr15-78981001;