rs11072773

Positions:

• chr15-78647233-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.46+2146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,092 control chromosomes in the GnomAD database, including 987 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 0.063 (987 hom., cov: 31)
• Consequence: CHRNB4 XM_011521186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB4	XM_011521186.3	c.46+2146G>A		intron_variant			XP_011519488.1
CHRNB4	XM_011521187.3	c.46+2146G>A		intron_variant			XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB4	ENST00000559849.5	c.46+2146G>A		intron_variant, NMD_transcript_variant		1		ENSP00000457404
CHRNB4	ENST00000560511.5	n.409+2146G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9562 AN: 151974 Hom.: 988 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0629 AC: 9567 AN: 152092 Hom.: 987 Cov.: 31 AF XY: 0.0602 AC XY: 4477 AN XY: 74368

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0431 Hom.: 90

Bravo AF: 0.0713

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11072773; hg19: chr15-78939575;