rs2565059

chr8-27479461-G-A

Variant summary

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

The ENST00000524096.5(CHRNA2):c.-137+308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,996 control chromosomes in the GnomAD database, including 3,399 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 0.21 (3399 hom., cov: 32)
• Consequence: CHRNA2 ENST00000524096.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA2	ENST00000520208.1	c.-433+308C>T		intron_variant		4
CHRNA2	ENST00000524096.5	c.-137+308C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31127 AN: 151878 Hom.: 3395 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.205 AC: 31167 AN: 151996 Hom.: 3399 Cov.: 32 AF XY: 0.207 AC XY: 15398 AN XY: 74270

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.176

Alfa AF: 0.198 Hom.: 4070

Bravo AF: 0.198

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.8
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2565059; hg19: chr8-27336978;