rs1996371

chr15-78664464-T-C

Variant summary

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

The ENST00000569846.1(ENSG00000290426):n.366+2930T>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 0.276 in 152,148 control chromosomes in the GnomAD database, including 7,446 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 0.28 (7446 hom., cov: 32)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 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.366+2930T>C		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-8801A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42007 AN: 152030 Hom.: 7443 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.276 AC: 42010 AN: 152148 Hom.: 7446 Cov.: 32 AF XY: 0.272 AC XY: 20196 AN XY: 74374

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.302

Alfa AF: 0.339 Hom.: 3370

Bravo AF: 0.261

Asia WGS AF: 0.116 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1996371; hg19: chr15-78956806;