rs6495314

Positions:

• chr15-78668187-A-C

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.366+6653A>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 0.347 in 152,100 control chromosomes in the GnomAD database, including 9,416 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 0.35 (9416 hom., cov: 33)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000569846.1	n.366+6653A>C		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-12524T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52699 AN: 151978 Hom.: 9415 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.347 AC: 52718 AN: 152100 Hom.: 9416 Cov.: 33 AF XY: 0.342 AC XY: 25438 AN XY: 74352

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.349

Alfa AF: 0.395 Hom.: 24495

Bravo AF: 0.341

Asia WGS AF: 0.274 AC: 959 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	1.4
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6495314; hg19: chr15-78960529;