15-78633093-A-G

Variant names:

• chr15-78633093-A-G
• rs4887072
• NM_000750.5:c.205-1761T>C

Variant summary

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

The ENST00000261751.8(CHRNB4):​c.205-1761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,078 control chromosomes in the GnomAD database, including 6,421 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 (6421 hom., cov: 32)
• Consequence: CHRNB4 ENST00000261751.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261751.8. 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
	CHRNB4	NM_000750.5	MANE Select	c.205-1761T>C		intron	N/A	NP_000741.1
	CHRNB4	NM_001256567.3		c.205-1761T>C		intron	N/A	NP_001243496.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000261751.8	TSL:1 MANE Select	c.205-1761T>C		intron	N/A	ENSP00000261751.3
	CHRNB4	ENST00000412074.6	TSL:1	c.205-1761T>C		intron	N/A	ENSP00000416386.2
	CHRNB4	ENST00000559849.5	TSL:1	n.*112+1529T>C		intron	N/A	ENSP00000457404.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41776 AN: 151960 Hom.: 6398 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.275 AC: 41840 AN: 152078 Hom.: 6421 Cov.: 32 AF XY: 0.283 AC XY: 21008 AN XY: 74342

African (AFR) AF: 0.261 AC: 10828 AN: 41474

American (AMR) AF: 0.438 AC: 6677 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2413 AN: 5164

South Asian (SAS) AF: 0.440 AC: 2118 AN: 4812

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10576

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15218 AN: 68002

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.253 Hom.: 1712

Bravo AF: 0.288

Asia WGS AF: 0.488 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-0.24
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: rs4887072; hg19: chr15-78925435;