rs1316971

chr15-78638168-A-Gchr15-78638168-A-T

Variant summary

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

The NM_000750.5(CHRNB4):c.56-2581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,090 control chromosomes in the GnomAD database, including 32,376 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 0.62 (32376 hom., cov: 33)
• Consequence: CHRNB4 NM_000750.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB4	NM_000750.5	c.56-2581T>C		intron_variant		ENST00000261751.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB4	ENST00000261751.8	c.56-2581T>C		intron_variant		1	NM_000750.5	P1
CHRNB4	ENST00000412074.6	c.56-2581T>C		intron_variant		1
CHRNB4	ENST00000559849.5	c.47-2581T>C		intron_variant, NMD_transcript_variant		1
CHRNB4	ENST00000560511.5	n.410-2581T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94123 AN: 151972 Hom.: 32370 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.619 AC: 94161 AN: 152090 Hom.: 32376 Cov.: 33 AF XY: 0.611 AC XY: 45456 AN XY: 74352

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.627

Alfa AF: 0.760 Hom.: 86513

Bravo AF: 0.587

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.13
Dann	Benign	0.37

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: rs1316971; hg19: chr15-78930510;