15-78688659-T-C

Position:

• chr15-78688659-T-C

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.367-4023T>C 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 0.0377 in 152,184 control chromosomes in the GnomAD database, including 756 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 0.038 (756 hom., cov: 31)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 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.367-4023T>C		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.228+19329A>G		intron_variant, non_coding_transcript_variant		3
CHRNB4	ENST00000560868.1	n.66-1260A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5719 AN: 152066 Hom.: 751 Cov.: 31

Gnomad AFR AF: 0.00983

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.00755

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0377 AC: 5737 AN: 152184 Hom.: 756 Cov.: 31 AF XY: 0.0427 AC XY: 3178 AN XY: 74398

Gnomad4 AFR AF: 0.00992

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.00755

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0139 Hom.: 228

Bravo AF: 0.0541

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.8
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2869550; hg19: chr15-78981001;