Variant 8-27459928-G-T 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.*1701C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,556 control chromosomes in the GnomAD database, including 14,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14352 hom., cov: 31)

Exomes 𝑓: 0.29 ( 28 hom. )

Consequence

CHRNA2
NM_000742.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.183

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=-0.91).

BP6

Variant 8-27459928-G-T is Benign according to our data. Variant chr8-27459928-G-T is described in ClinVar as [Benign]. Clinvar id is 362665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA2	NM_000742.4 linkuse as main transcript	c.*1701C>A		3_prime_UTR_variant	7/7	ENST00000407991.3	NP_000733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA2	ENST00000407991.3 linkuse as main transcript	c.*1701C>A		3_prime_UTR_variant	7/7	5	NM_000742.4	ENSP00000385026	P2	Q15822-1

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64095

AN:

151814

Hom.:

14340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.285

AC:

178

AN:

624

Hom.:

Cov.:

AF XY:

0.300

AC XY:

137

AN XY:

456

show subpopulations

Gnomad4 AFR exome

AF:

0.643

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.0714

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.422

AC:

64127

AN:

151932

Hom.:

14352

Cov.:

AF XY:

0.417

AC XY:

30927

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.568

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.387

Hom.:

9310

Bravo

AF:

0.434

Asia WGS

AF:

0.341

AC:

1189

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal dominant nocturnal frontal lobe epilepsy 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

DANN

Benign

0.51

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