Variant rs735421 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000742.4(CHRNA2):c.1465-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,550 control chromosomes in the GnomAD database, including 80,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6435 hom., cov: 33)

Exomes 𝑓: 0.31 ( 73884 hom. )

Consequence

CHRNA2
NM_000742.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.240

Variant links:

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]

CHRNA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-27461775-A-G is Benign according to our data. Variant chr8-27461775-A-G is described in ClinVar as [Benign]. Clinvar id is 670848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA2	NM_000742.4 link	c.1465-21T>C		intron_variant	Intron 6 of 6	ENST00000407991.3	NP_000733.2	Q15822-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA2	ENST00000407991.3 link	c.1465-21T>C		intron_variant	Intron 6 of 6	5	NM_000742.4	ENSP00000385026.1		Q15822-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41334

AN:

152086

Hom.:

6429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.294

GnomAD3 exomes

AF:

0.310

AC:

77683

AN:

250436

Hom.:

12662

AF XY:

0.310

AC XY:

41992

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.315

AC:

459696

AN:

1461346

Hom.:

73884

Cov.:

AF XY:

0.314

AC XY:

228139

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.272

AC:

41357

AN:

152204

Hom.:

6435

Cov.:

AF XY:

0.274

AC XY:

20412

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.376

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.325

Hom.:

8487

Bravo

AF:

0.262

Asia WGS

AF:

0.224

AC:

779

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.6

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over