rs6495316

Variant names:

• chr15-78693759-T-A
• rs6495316
• ENST00000558216.1:n.262-865A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78693759-T-A
• chr15-78693759-T-C
• chr15-78693759-T-G

Variant summary

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

The ENST00000558216.1(CHRNB4):​n.262-865A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,082 control chromosomes in the GnomAD database, including 57,670 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 0.85 (57670 hom., cov: 30)
• Consequence: CHRNB4 ENST00000558216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105370913	XR_932508.2	n.1466-865A>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932509.2	n.1422-865A>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932510.3	n.568-865A>T		intron_variant	Intron 2 of 2
LOC105370913	XR_932511.3	n.376-865A>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000558216.1	n.262-865A>T		intron_variant	Intron 2 of 2	2
CHRNB4	ENST00000560511.5	n.228+14229A>T		intron_variant	Intron 2 of 6	3
CHRNB4	ENST00000560868.1	n.66-6360A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129262 AN: 151964 Hom.: 57633 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.851 AC: 129353 AN: 152082 Hom.: 57670 Cov.: 30 AF XY: 0.854 AC XY: 63458 AN XY: 74350

African (AFR) AF: 0.550 AC: 22768 AN: 41396

American (AMR) AF: 0.932 AC: 14247 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3348 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4625 AN: 5164

South Asian (SAS) AF: 0.947 AC: 4571 AN: 4828

European-Finnish (FIN) AF: 0.967 AC: 10241 AN: 10586

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66611 AN: 68026

Other (OTH) AF: 0.881 AC: 1862 AN: 2114

Alfa AF: 0.905 Hom.: 7971

Bravo AF: 0.833

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs6495316; hg19: chr15-78986101;