15-78682203-A-G

Variant names:

• chr15-78682203-A-G
• rs8038920
• ENST00000560511.5:n.228+25785T>C

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.228+25785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,096 control chromosomes in the GnomAD database, including 29,732 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 0.62 (29732 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• 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

ENSG00000290426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560511.5. 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	ENST00000560511.5	TSL:3	n.228+25785T>C		intron	N/A
	ENSG00000290426	ENST00000569846.2	TSL:4	n.367-10479A>G		intron	N/A
	ENSG00000290426	ENST00000846725.1		n.401-10479A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94660 AN: 151978 Hom.: 29706 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.623 AC: 94720 AN: 152096 Hom.: 29732 Cov.: 32 AF XY: 0.626 AC XY: 46545 AN XY: 74358

African (AFR) AF: 0.530 AC: 21975 AN: 41480

American (AMR) AF: 0.700 AC: 10705 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3470

East Asian (EAS) AF: 0.576 AC: 2975 AN: 5168

South Asian (SAS) AF: 0.688 AC: 3313 AN: 4818

European-Finnish (FIN) AF: 0.706 AC: 7474 AN: 10586

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43981 AN: 67972

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.641 Hom.: 60564

Bravo AF: 0.617

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.054
DANN	Benign	0.75
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs8038920; hg19: chr15-78974545;