15-78691217-C-T

Variant names:

• chr15-78691217-C-T
• rs11638372
• ENST00000560511.5:n.228+16771G>A

Variant summary

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

The ENST00000560868.1(CHRNB4):​n.66-3818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,176 control chromosomes in the GnomAD database, including 7,372 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 0.28 (7372 hom., cov: 33)
• Consequence: CHRNB4 ENST00000560868.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000560511.5	n.228+16771G>A		intron_variant	Intron 2 of 6	3
CHRNB4	ENST00000560868.1	n.66-3818G>A		intron_variant	Intron 1 of 1	2
ENSG00000290426	ENST00000569846.2	n.367-1465C>T		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42245 AN: 152058 Hom.: 7368 Cov.: 33

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.278 AC: 42255 AN: 152176 Hom.: 7372 Cov.: 33 AF XY: 0.272 AC XY: 20239 AN XY: 74412

African (AFR) AF: 0.0917 AC: 3809 AN: 41516

American (AMR) AF: 0.257 AC: 3933 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5178

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3421 AN: 10588

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27629 AN: 67976

Other (OTH) AF: 0.299 AC: 632 AN: 2116

Alfa AF: 0.362 Hom.: 10193

Bravo AF: 0.265

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		0.69

Splicing

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

Other links and lift over

dbSNP: rs11638372; hg19: chr15-78983559;