rs8032156

Positions:

• chr15-78672156-A-G
• chr15-78672156-A-T

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.366+10622A>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 0.751 in 152,106 control chromosomes in the GnomAD database, including 43,513 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 0.75 (43513 hom., cov: 33)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 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+10622A>G		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-16493T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114179 AN: 151988 Hom.: 43493 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.751 AC: 114236 AN: 152106 Hom.: 43513 Cov.: 33 AF XY: 0.741 AC XY: 55091 AN XY: 74356

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.744

Alfa AF: 0.807 Hom.: 97548

Bravo AF: 0.746

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8032156; hg19: chr15-78964498;