chr15-78636604-G-T

Position:

• chr15-78636604-G-T

Variant summary

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

The NM_000750.5(CHRNB4):​c.56-1017C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 149,836 control chromosomes in the GnomAD database, including 9,210 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 0.35 (9210 hom., cov: 30)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	NM_000750.5	c.56-1017C>A		intron_variant		ENST00000261751.8	NP_000741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000261751.8	c.56-1017C>A		intron_variant		1	NM_000750.5	ENSP00000261751	P1
CHRNB4	ENST00000412074.6	c.56-1017C>A		intron_variant		1		ENSP00000416386
CHRNB4	ENST00000559849.5	c.47-1017C>A		intron_variant, NMD_transcript_variant		1		ENSP00000457404
CHRNB4	ENST00000560511.5	n.410-1017C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52045 AN: 149746 Hom.: 9208 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.347 AC: 52067 AN: 149836 Hom.: 9210 Cov.: 30 AF XY: 0.342 AC XY: 24993 AN XY: 72980

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.328

Alfa AF: 0.370 Hom.: 7140

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11636753; hg19: chr15-78928946;