chr15-78656785-C-T

Variant names:

• chr15-78656785-C-T
• rs12900519
• ENST00000559849.5:n.-708-95G>A

Variant summary

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

The ENST00000559849.5(CHRNB4):​n.-708-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,156 control chromosomes in the GnomAD database, including 59,172 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 0.88 (59172 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CHRNB4 ENST00000559849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB4	ENST00000559849.5	TSL:1	n.-708-95G>A		intron	N/A	ENSP00000457404.1
	CHRNB4	ENST00000560511.5	TSL:3	n.229-1122G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133809 AN: 152032 Hom.: 59146 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.880 AC: 133895 AN: 152152 Hom.: 59172 Cov.: 31 AF XY: 0.877 AC XY: 65205 AN XY: 74388

African (AFR) AF: 0.811 AC: 33648 AN: 41472

American (AMR) AF: 0.870 AC: 13301 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3181 AN: 3472

East Asian (EAS) AF: 0.772 AC: 3992 AN: 5168

South Asian (SAS) AF: 0.925 AC: 4464 AN: 4828

European-Finnish (FIN) AF: 0.862 AC: 9122 AN: 10586

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

European-Non Finnish (NFE) AF: 0.929 AC: 63185 AN: 68016

Other (OTH) AF: 0.884 AC: 1868 AN: 2114

Alfa AF: 0.918 Hom.: 115141

Bravo AF: 0.877

Asia WGS AF: 0.828 AC: 2882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs12900519; hg19: chr15-78949127;