rs7166158

Positions:

• chr15-78656411-T-A
• chr15-78656411-T-G

Variant summary

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

The XM_011521186.3(CHRNB4):​c.-229-748A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 151,164 control chromosomes in the GnomAD database, including 60,476 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 (60476 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: CHRNB4 XM_011521186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	XM_011521186.3	c.-229-748A>T		intron_variant			XP_011519488.1
CHRNB4	XM_011521187.3	c.-135-748A>T		intron_variant			XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000559849.5	c.-429A>T		5_prime_UTR_variant, NMD_transcript_variant	4/12	1		ENSP00000457404
CHRNB4	ENST00000560511.5	n.229-748A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.894 AC: 134972 AN: 151048 Hom.: 60442 Cov.: 27

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.896

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.894 AC: 135066 AN: 151164 Hom.: 60476 Cov.: 27 AF XY: 0.889 AC XY: 65572 AN XY: 73736

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.894

Alfa AF: 0.890 Hom.: 2864

Bravo AF: 0.892

Asia WGS AF: 0.833 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7166158; hg19: chr15-78948753;