rs9920506

Variant names:

• chr15-78638715-A-G
• rs9920506
• NM_000750.5:c.55+2364T>C

Variant summary

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

The NM_000750.5(CHRNB4):​c.55+2364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,144 control chromosomes in the GnomAD database, including 47,687 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 0.79 (47687 hom., cov: 33)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB4	NM_000750.5	c.55+2364T>C		intron_variant	Intron 1 of 5	ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000261751.8	c.55+2364T>C		intron_variant	Intron 1 of 5	1	NM_000750.5	ENSP00000261751.3
CHRNB4	ENST00000412074.6	c.55+2364T>C		intron_variant	Intron 1 of 4	1		ENSP00000416386.2
CHRNB4	ENST00000559849.5	n.47-3128T>C		intron_variant	Intron 7 of 11	1		ENSP00000457404.1
CHRNB4	ENST00000560511.5	n.410-3128T>C		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119398 AN: 152026 Hom.: 47661 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.785 AC: 119467 AN: 152144 Hom.: 47687 Cov.: 33 AF XY: 0.775 AC XY: 57644 AN XY: 74370

African (AFR) AF: 0.809 AC: 33573 AN: 41506

American (AMR) AF: 0.599 AC: 9151 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2784 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2883 AN: 5152

South Asian (SAS) AF: 0.587 AC: 2832 AN: 4828

European-Finnish (FIN) AF: 0.771 AC: 8166 AN: 10590

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57552 AN: 68004

Other (OTH) AF: 0.764 AC: 1611 AN: 2108

Alfa AF: 0.808 Hom.: 7828

Bravo AF: 0.769

Asia WGS AF: 0.552 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-2.0
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: rs9920506; hg19: chr15-78931057;