rs922692

Positions:

• chr15-78691872-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000569846.1(ENSG00000290426):​n.367-810C>A variant causes a intron, non coding transcript 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: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000569846.1	n.367-810C>A		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.228+16116G>T		intron_variant, non_coding_transcript_variant		3
CHRNB4	ENST00000560868.1	n.66-4473G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.296

Alfa AF: 0.326 Hom.: 1121

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs922692; hg19: chr15-78984214;