rs3813567

chr15-78642209-G-Achr15-78642209-G-Cchr15-78642209-G-T

Variant summary

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

The ENST00000559849.5(CHRNB4):c.47-6622C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,122 control chromosomes in the GnomAD database, including 44,313 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 0.76 (44313 hom., cov: 34)
• Consequence: CHRNB4 ENST00000559849.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB4	XM_011521186.3	c.47-6622C>T		intron_variant
CHRNB4	XM_011521187.3	c.47-6622C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB4	ENST00000559849.5	c.47-6622C>T		intron_variant, NMD_transcript_variant		1
CHRNB4	ENST00000560511.5	n.410-6622C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115447 AN: 152004 Hom.: 44291 Cov.: 34

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.759 AC: 115516 AN: 152122 Hom.: 44313 Cov.: 34 AF XY: 0.749 AC XY: 55726 AN XY: 74358

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.731

Alfa AF: 0.781 Hom.: 5484

Bravo AF: 0.753

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813567; hg19: chr15-78934551;