rs8043123

Positions:

• chr15-78681051-C-T

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.367-11631C>T 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 0.267 in 152,166 control chromosomes in the GnomAD database, including 6,040 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 (6040 hom., cov: 33)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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.367-11631C>T		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-25388G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40545 AN: 152050 Hom.: 6025 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.267 AC: 40581 AN: 152166 Hom.: 6040 Cov.: 33 AF XY: 0.277 AC XY: 20634 AN XY: 74384

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.285

Alfa AF: 0.303 Hom.: 1829

Bravo AF: 0.264

Asia WGS AF: 0.482 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8043123; hg19: chr15-78973393;