ENST00000560511.5:n.229-8801A>G

Variant names:

• chr15-78664464-T-C
• rs1996371
• ENST00000560511.5:n.229-8801A>G

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.229-8801A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,148 control chromosomes in the GnomAD database, including 7,446 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 0.28 (7446 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 27 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000560511.5	n.229-8801A>G		intron_variant	Intron 2 of 6	3
ENSG00000290426	ENST00000569846.2	n.366+2930T>C		intron_variant	Intron 2 of 5	4
ENSG00000290426	ENST00000846725.1	n.400+2930T>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42007 AN: 152030 Hom.: 7443 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.276 AC: 42010 AN: 152148 Hom.: 7446 Cov.: 32 AF XY: 0.272 AC XY: 20196 AN XY: 74374

African (AFR) AF: 0.0795 AC: 3302 AN: 41534

American (AMR) AF: 0.253 AC: 3867 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3470

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5180

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4808

European-Finnish (FIN) AF: 0.347 AC: 3670 AN: 10580

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27639 AN: 67980

Other (OTH) AF: 0.302 AC: 638 AN: 2110

Alfa AF: 0.342 Hom.: 7271

Bravo AF: 0.261

Asia WGS AF: 0.116 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.84
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs1996371; hg19: chr15-78956806;