rs6495314

Variant names:

• chr15-78668187-A-C
• rs6495314
• ENST00000560511.5:n.229-12524T>G

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.229-12524T>G 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 152,100 control chromosomes in the GnomAD database, including 9,416 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 (9416 hom., cov: 33)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 23 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

ENSG00000290426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000560511.5	n.229-12524T>G		intron_variant	Intron 2 of 6	3
ENSG00000290426	ENST00000569846.2	n.366+6653A>C		intron_variant	Intron 2 of 5	4
ENSG00000290426	ENST00000846725.1	n.400+6653A>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52699 AN: 151978 Hom.: 9415 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.347 AC: 52718 AN: 152100 Hom.: 9416 Cov.: 33 AF XY: 0.342 AC XY: 25438 AN XY: 74352

African (AFR) AF: 0.273 AC: 11337 AN: 41484

American (AMR) AF: 0.275 AC: 4200 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1357 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2076 AN: 5172

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4826

European-Finnish (FIN) AF: 0.348 AC: 3679 AN: 10582

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27716 AN: 67972

Other (OTH) AF: 0.349 AC: 737 AN: 2112

Alfa AF: 0.383 Hom.: 36804

Bravo AF: 0.341

Asia WGS AF: 0.274 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.38
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs6495314; hg19: chr15-78960529;