chr15-78643134-T-C

Variant names:

• chr15-78643134-T-C
• rs11633223
• ENST00000559849.5:n.46+6245A>G

Variant summary

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

The ENST00000559849.5(CHRNB4):​n.46+6245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 143,750 control chromosomes in the GnomAD database, including 7,523 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 0.31 (7523 hom., cov: 32)
• Consequence: CHRNB4 ENST00000559849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 18 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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000559849.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000559849.5	TSL:1	n.46+6245A>G		intron	N/A	ENSP00000457404.1	H3BU02
	CHRNB4	ENST00000560511.5	TSL:3	n.409+6245A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.314 AC: 45084 AN: 143650 Hom.: 7526 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.314 AC: 45077 AN: 143750 Hom.: 7523 Cov.: 32 AF XY: 0.308 AC XY: 21689 AN XY: 70410

African (AFR) AF: 0.206 AC: 6924 AN: 33560

American (AMR) AF: 0.224 AC: 3369 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1280 AN: 3384

East Asian (EAS) AF: 0.0981 AC: 509 AN: 5190

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10566

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27052 AN: 67944

Other (OTH) AF: 0.295 AC: 601 AN: 2036

Alfa AF: 0.362 Hom.: 9049

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs11633223; hg19: chr15-78935476;