rs3813567

Variant names:

• chr15-78642209-G-A
• rs3813567
• ENST00000559849.5:n.47-6622C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78642209-G-A
• chr15-78642209-G-C
• chr15-78642209-G-T

Variant summary

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

The ENST00000559849.5(CHRNB4):​n.47-6622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,122 control chromosomes in the GnomAD database, including 44,313 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 0.76 (44313 hom., cov: 34)
• Consequence: CHRNB4 ENST00000559849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 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.47-6622C>T		intron	N/A	ENSP00000457404.1	H3BU02
	CHRNB4	ENST00000560511.5	TSL:3	n.410-6622C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115447 AN: 152004 Hom.: 44291 Cov.: 34

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.759 AC: 115516 AN: 152122 Hom.: 44313 Cov.: 34 AF XY: 0.749 AC XY: 55726 AN XY: 74358

African (AFR) AF: 0.796 AC: 33004 AN: 41460

American (AMR) AF: 0.633 AC: 9679 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2728 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3087 AN: 5178

South Asian (SAS) AF: 0.556 AC: 2677 AN: 4812

European-Finnish (FIN) AF: 0.691 AC: 7313 AN: 10582

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54631 AN: 68010

Other (OTH) AF: 0.731 AC: 1543 AN: 2112

Alfa AF: 0.782 Hom.: 68931

Bravo AF: 0.753

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs3813567; hg19: chr15-78934551;