15-78660789-C-T

Position:

• chr15-78660789-C-T

Variant summary

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

The XM_011521186.3(CHRNB4):​c.-597G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 233,418 control chromosomes in the GnomAD database, including 94,295 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 0.89 (60703 hom., cov: 32)
  • Exomes 𝑓: 0.91 (33592 hom.)
• Consequence: CHRNB4 XM_011521186.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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]

ENSG00000290426 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	XM_011521186.3	c.-597G>A		5_prime_UTR_variant	1/10		XP_011519488.1
CHRNB4	XM_011521187.3	c.-503G>A		5_prime_UTR_variant	1/9		XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000290426	ENST00000569846.1	n.146C>T		non_coding_transcript_exon_variant	1/4	4
CHRNB4	ENST00000560511.5	n.229-5126G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135680 AN: 152130 Hom.: 60677 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.896

GnomAD4 exome AF: 0.908 AC: 73738 AN: 81168 Hom.: 33592 Cov.: 0 AF XY: 0.911 AC XY: 38504 AN XY: 42266

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.922

Gnomad4 ASJ exome AF: 0.924

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.901

GnomAD4 genome AF: 0.892 AC: 135765 AN: 152250 Hom.: 60703 Cov.: 32 AF XY: 0.889 AC XY: 66173 AN XY: 74434

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.894

Alfa AF: 0.906 Hom.: 7756

Bravo AF: 0.893

Asia WGS AF: 0.845 AC: 2942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4887075; hg19: chr15-78953131;