Variant 8-27464080-G-C 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.450-87C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,517,462 control chromosomes in the GnomAD database, including 543,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51568 hom., cov: 31)

Exomes 𝑓: 0.85 ( 491788 hom. )

Consequence

CHRNA2
NM_000742.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 8-27464080-G-C is Benign according to our data. Variant chr8-27464080-G-C is described in ClinVar as [Benign]. Clinvar id is 670757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA2	NM_000742.4 linkuse as main transcript	c.450-87C>G		intron_variant		ENST00000407991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA2	ENST00000407991.3 linkuse as main transcript	c.450-87C>G		intron_variant		5	NM_000742.4	P2	Q15822-1

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124736

AN:

151988

Hom.:

51536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.935

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.846

GnomAD4 exome

AF:

0.847

AC:

1156463

AN:

1365356

Hom.:

491788

AF XY:

0.848

AC XY:

576511

AN XY:

679882

show subpopulations

Gnomad4 AFR exome

AF:

0.776

Gnomad4 AMR exome

AF:

0.809

Gnomad4 ASJ exome

AF:

0.925

Gnomad4 EAS exome

AF:

0.573

Gnomad4 SAS exome

AF:

0.868

Gnomad4 FIN exome

AF:

0.836

Gnomad4 NFE exome

AF:

0.857

Gnomad4 OTH exome

AF:

0.846

GnomAD4 genome

AF:

0.821

AC:

124820

AN:

152106

Hom.:

51568

Cov.:

AF XY:

0.818

AC XY:

60823

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.808

Gnomad4 ASJ

AF:

0.935

Gnomad4 EAS

AF:

0.554

Gnomad4 SAS

AF:

0.849

Gnomad4 FIN

AF:

0.836

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.847

Alfa

AF:

0.811

Hom.:

2556

Bravo

AF:

0.817

Asia WGS

AF:

0.716

AC:

2490

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

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 54% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 50. Only high quality variants are reported. -

Autosomal dominant nocturnal frontal lobe epilepsy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.81

DANN

Benign

0.56

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