Variant rs9333567 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000682.7(ADRA2B):c.36A>G(p.Thr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,611,556 control chromosomes in the GnomAD database, including 3,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.057 ( 369 hom., cov: 33)

Exomes 𝑓: 0.048 ( 2655 hom. )

Consequence

ADRA2B
NM_000682.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.14

Variant links:

Genes affected

ADRA2B (HGNC:282): (adrenoceptor alpha 2B) This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

ADRA2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-96116114-T-C is Benign according to our data. Variant chr2-96116114-T-C is described in ClinVar as [Benign]. Clinvar id is 3035382.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7 linkuse as main transcript	c.36A>G	p.Thr12=	synonymous_variant	1/1	ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2 linkuse as main transcript	c.36A>G	p.Thr12=	synonymous_variant	1/1		NM_000682.7	ENSP00000480573	P1

Frequencies

GnomAD3 genomes

AF:

0.0569

AC:

8655

AN:

152118

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0363

Gnomad OTH

AF:

0.0589

GnomAD3 exomes

AF:

0.0693

AC:

16741

AN:

241692

Hom.:

1062

AF XY:

0.0628

AC XY:

8293

AN XY:

132078

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.181

Gnomad SAS exome

AF:

0.0348

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0386

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0481

AC:

70141

AN:

1459320

Hom.:

2655

Cov.:

AF XY:

0.0470

AC XY:

34139

AN XY:

725860

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.0553

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.0368

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0394

Gnomad4 OTH exome

AF:

0.0615

GnomAD4 genome

AF:

0.0570

AC:

8683

AN:

152236

Hom.:

369

Cov.:

AF XY:

0.0568

AC XY:

4224

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0680

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.0479

Gnomad4 FIN

AF:

0.0270

Gnomad4 NFE

AF:

0.0363

Gnomad4 OTH

AF:

0.0597

Alfa

AF:

0.0512

Hom.:

213

Bravo

AF:

0.0666

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADRA2B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

DANN

Benign

0.48

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