rs11636753

Variant names:

• chr15-78636604-G-T
• rs11636753
• NM_000750.5:c.56-1017C>A

Variant summary

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

The NM_000750.5(CHRNB4):​c.56-1017C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 149,836 control chromosomes in the GnomAD database, including 9,210 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 0.35 (9210 hom., cov: 30)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 27 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000750.5. 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
	CHRNB4	NM_000750.5	MANE Select	c.56-1017C>A		intron	N/A	NP_000741.1
	CHRNB4	NM_001256567.3		c.56-1017C>A		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.56-1017C>A		intron	N/A	ENSP00000261751.3
	CHRNB4	ENST00000412074.6	TSL:1	c.56-1017C>A		intron	N/A	ENSP00000416386.2
	CHRNB4	ENST00000559849.5	TSL:1	n.47-1017C>A		intron	N/A	ENSP00000457404.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52045 AN: 149746 Hom.: 9208 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.347 AC: 52067 AN: 149836 Hom.: 9210 Cov.: 30 AF XY: 0.342 AC XY: 24993 AN XY: 72980

African (AFR) AF: 0.310 AC: 12619 AN: 40690

American (AMR) AF: 0.245 AC: 3688 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1333 AN: 3448

East Asian (EAS) AF: 0.183 AC: 931 AN: 5084

South Asian (SAS) AF: 0.297 AC: 1403 AN: 4728

European-Finnish (FIN) AF: 0.350 AC: 3505 AN: 10026

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27440 AN: 67558

Other (OTH) AF: 0.328 AC: 682 AN: 2082

Alfa AF: 0.376 Hom.: 10325

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.28
PhyloP100		-1.3
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: rs11636753; hg19: chr15-78928946;