rs12905641

Positions:

• chr15-78672020-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000569846.1(ENSG00000290426):​n.366+10486C>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 0.292 in 152,202 control chromosomes in the GnomAD database, including 6,598 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 0.29 (6598 hom., cov: 34)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000569846.1	n.366+10486C>T		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-16357G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44467 AN: 152084 Hom.: 6597 Cov.: 34

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.292 AC: 44488 AN: 152202 Hom.: 6598 Cov.: 34 AF XY: 0.289 AC XY: 21473 AN XY: 74426

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.289

Alfa AF: 0.298 Hom.: 2183

Bravo AF: 0.284

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12905641; hg19: chr15-78964362;