15-78682203-A-G

Position:

• chr15-78682203-A-G

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.367-10479A>G 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 0.623 in 152,096 control chromosomes in the GnomAD database, including 29,732 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 (29732 hom., cov: 32)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 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.367-10479A>G		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.228+25785T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94660 AN: 151978 Hom.: 29706 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.623 AC: 94720 AN: 152096 Hom.: 29732 Cov.: 32 AF XY: 0.626 AC XY: 46545 AN XY: 74358

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.651

Alfa AF: 0.643 Hom.: 43227

Bravo AF: 0.617

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.054
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8038920; hg19: chr15-78974545;