chr15-78649693-T-C

Variant names:

• chr15-78649693-T-C
• rs3971872
• ENST00000559849.5:n.-15-254A>G

Variant summary

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

The ENST00000559849.5(CHRNB4):​n.-15-254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,194 control chromosomes in the GnomAD database, including 60,146 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 0.89 (60146 hom., cov: 32)
• Consequence: CHRNB4 ENST00000559849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000559849.5	TSL:1	n.-15-254A>G		intron	N/A	ENSP00000457404.1
	CHRNB4	ENST00000560511.5	TSL:3	n.349-254A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135129 AN: 152076 Hom.: 60110 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.889 AC: 135225 AN: 152194 Hom.: 60146 Cov.: 32 AF XY: 0.886 AC XY: 65880 AN XY: 74386

African (AFR) AF: 0.854 AC: 35477 AN: 41520

American (AMR) AF: 0.892 AC: 13643 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3162 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4193 AN: 5172

South Asian (SAS) AF: 0.913 AC: 4402 AN: 4824

European-Finnish (FIN) AF: 0.861 AC: 9107 AN: 10580

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62291 AN: 68014

Other (OTH) AF: 0.892 AC: 1885 AN: 2114

Alfa AF: 0.911 Hom.: 123566

Bravo AF: 0.890

Asia WGS AF: 0.835 AC: 2904 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs3971872; hg19: chr15-78942035;