rs922692

Variant names:

• chr15-78691872-C-A
• rs922692
• ENST00000560511.5:n.228+16116G>T

Variant summary

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

The ENST00000560511.5(CHRNB4):​n.228+16116G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,142 control chromosomes in the GnomAD database, including 7,326 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 0.27 (7326 hom., cov: 32)
• Consequence: CHRNB4 ENST00000560511.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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

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 (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.228+16116G>T		intron_variant	Intron 2 of 6	3
CHRNB4	ENST00000560868.1	n.66-4473G>T		intron_variant	Intron 1 of 1	2
ENSG00000290426	ENST00000569846.2	n.367-810C>A		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41746 AN: 152024 Hom.: 7322 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.274 AC: 41750 AN: 152142 Hom.: 7326 Cov.: 32 AF XY: 0.269 AC XY: 20004 AN XY: 74384

African (AFR) AF: 0.0804 AC: 3338 AN: 41538

American (AMR) AF: 0.255 AC: 3904 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1201 AN: 3464

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5182

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3420 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27630 AN: 67968

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.317 Hom.: 1129

Bravo AF: 0.262

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.86
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs922692; hg19: chr15-78984214;