rs12440014

Variant names:

• chr15-78634384-C-G
• rs12440014
• NM_000750.5:c.204+1055G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-78634384-C-G
• chr15-78634384-C-T

Variant summary

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

The NM_000750.5(CHRNB4):​c.204+1055G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,196 control chromosomes in the GnomAD database, including 6,230 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 0.27 (6230 hom., cov: 33)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB4	NM_000750.5	c.204+1055G>C		intron_variant	Intron 2 of 5	ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000261751.8	c.204+1055G>C		intron_variant	Intron 2 of 5	1	NM_000750.5	ENSP00000261751.3
CHRNB4	ENST00000412074.6	c.204+1055G>C		intron_variant	Intron 2 of 4	1		ENSP00000416386.2
CHRNB4	ENST00000559849.5	n.*112+238G>C		intron_variant	Intron 9 of 11	1		ENSP00000457404.1
CHRNB4	ENST00000560511.5	n.558+1055G>C		intron_variant	Intron 5 of 6	3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41109 AN: 152078 Hom.: 6213 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.270 AC: 41156 AN: 152196 Hom.: 6230 Cov.: 33 AF XY: 0.278 AC XY: 20694 AN XY: 74416

African (AFR) AF: 0.225 AC: 9335 AN: 41524

American (AMR) AF: 0.445 AC: 6808 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2336 AN: 5170

South Asian (SAS) AF: 0.446 AC: 2149 AN: 4818

European-Finnish (FIN) AF: 0.288 AC: 3057 AN: 10612

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15862 AN: 67990

Other (OTH) AF: 0.281 AC: 595 AN: 2114

Alfa AF: 0.253 Hom.: 663

Bravo AF: 0.283

Asia WGS AF: 0.485 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.6
DANN	Benign	0.78
PhyloP100		-1.0
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: rs12440014; hg19: chr15-78926726;