chr15-78643134-T-C

Position:

• chr15-78643134-T-C

Variant summary

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

The ENST00000559849.5(CHRNB4):​c.46+6245A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 143,750 control chromosomes in the GnomAD database, including 7,523 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 0.31 (7523 hom., cov: 32)
• Consequence: CHRNB4 ENST00000559849.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	XM_011521186.3	c.46+6245A>G		intron_variant			XP_011519488.1
CHRNB4	XM_011521187.3	c.46+6245A>G		intron_variant			XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000559849.5	c.46+6245A>G		intron_variant, NMD_transcript_variant		1		ENSP00000457404
CHRNB4	ENST00000560511.5	n.409+6245A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 45084 AN: 143650 Hom.: 7526 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.314 AC: 45077 AN: 143750 Hom.: 7523 Cov.: 32 AF XY: 0.308 AC XY: 21689 AN XY: 70410

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.0981

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.295

Alfa AF: 0.366 Hom.: 8234

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.96

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11633223; hg19: chr15-78935476;