rs11072793

chr15-78714100-G-A

Variant summary

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

The XR_932509.2(LOC105370913):n.1304-5995C>T 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 0.583 in 152,026 control chromosomes in the GnomAD database, including 28,567 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 0.58 (28567 hom., cov: 32)
• Consequence: LOC105370913 XR_932509.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

LOC105370913 (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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105370913	XR_932509.2	n.1304-5995C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932508.2	n.1348-5995C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932510.3	n.449+1512C>T		intron_variant, non_coding_transcript_variant
LOC105370913	XR_932511.3	n.257+4268C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB4	ENST00000558216.1	n.144-5995C>T		intron_variant, non_coding_transcript_variant		2
CHRNB4	ENST00000560511.5	n.111-5995C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000565476.5	n.317-5205G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88645 AN: 151908 Hom.: 28565 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.583 AC: 88663 AN: 152026 Hom.: 28567 Cov.: 32 AF XY: 0.578 AC XY: 42916 AN XY: 74288

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.595

Alfa AF: 0.720 Hom.: 56008

Bravo AF: 0.572

Asia WGS AF: 0.455 AC: 1584 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	0.65
Dann	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11072793; hg19: chr15-79006442;