rs891397

chr8-27466850-C-A

Variant summary

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

The NM_000742.4(CHRNA2):c.449+379G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,122 control chromosomes in the GnomAD database, including 2,776 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 0.18 (2776 hom., cov: 33)
• Consequence: CHRNA2 NM_000742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA2	NM_000742.4	c.449+379G>T		intron_variant		ENST00000407991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA2	ENST00000407991.3	c.449+379G>T		intron_variant		5	NM_000742.4	P2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27137 AN: 152004 Hom.: 2766 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.179 AC: 27172 AN: 152122 Hom.: 2776 Cov.: 33 AF XY: 0.181 AC XY: 13470 AN XY: 74348

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0547

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.156

Alfa AF: 0.155 Hom.: 264

Bravo AF: 0.183

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs891397; hg19: chr8-27324367; COSMIC: COSV53558315; COSMIC: COSV53558315;