rs922691

Positions:

• chr15-78671652-A-G

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.366+10118A>G 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 0.3 in 152,186 control chromosomes in the GnomAD database, including 6,960 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 0.30 (6960 hom., cov: 32)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 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.366+10118A>G		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-15989T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45592 AN: 152068 Hom.: 6960 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.300 AC: 45612 AN: 152186 Hom.: 6960 Cov.: 32 AF XY: 0.295 AC XY: 21962 AN XY: 74408

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.297

Alfa AF: 0.337 Hom.: 17779

Bravo AF: 0.291

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs922691; hg19: chr15-78963994;