rs9314347

Positions:

• chr8-27462288-A-G

Variant summary

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

The NM_000742.4(CHRNA2):​c.1465-534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,242 control chromosomes in the GnomAD database, including 469 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 0.074 (469 hom., cov: 33)
• Consequence: CHRNA2 NM_000742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

Genes affected

CHRNA2 (HGNC:1956): (cholinergic receptor nicotinic alpha 2 subunit) Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA2	NM_000742.4	c.1465-534T>C		intron_variant		ENST00000407991.3	NP_000733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA2	ENST00000407991.3	c.1465-534T>C		intron_variant		5	NM_000742.4	ENSP00000385026.1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11219 AN: 152124 Hom.: 465 Cov.: 33

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0737 AC: 11225 AN: 152242 Hom.: 469 Cov.: 33 AF XY: 0.0758 AC XY: 5645 AN XY: 74430

Gnomad4 AFR AF: 0.0648

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0738 Hom.: 609

Bravo AF: 0.0669

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9314347; hg19: chr8-27319805;