chr15-78643077-C-G

Variant names:

• chr15-78643077-C-G
• rs11637890
• ENST00000559849.5:n.46+6302G>C

Variant summary

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

The ENST00000559849.5(CHRNB4):​n.46+6302G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,608 control chromosomes in the GnomAD database, including 7,525 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 0.30 (7525 hom., cov: 32)
• Consequence: CHRNB4 ENST00000559849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 13 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=-0.8).
• 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+6302G>C		intron	N/A	ENSP00000457404.1	H3BU02
	CHRNB4	ENST00000560511.5	TSL:3	n.409+6302G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45049 AN: 151488 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.297 AC: 45042 AN: 151608 Hom.: 7525 Cov.: 32 AF XY: 0.293 AC XY: 21676 AN XY: 74054

African (AFR) AF: 0.167 AC: 6910 AN: 41492

American (AMR) AF: 0.220 AC: 3365 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3472

East Asian (EAS) AF: 0.108 AC: 509 AN: 4730

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3553 AN: 10558

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27031 AN: 67952

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.350 Hom.: 1240

Bravo AF: 0.277

Asia WGS AF: 0.195 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.21
DANN	Benign	0.65
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs11637890; hg19: chr15-78935419;