rs9333567

chr2-96116114-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.057 (369 hom., cov: 33)
  • Exomes 𝑓: 0.048 (2655 hom.)
• Consequence: ADRA2B NM_000682.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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	UniProt
ADRA2B	NM_000682.7	c.36A>G	p.Thr12=	synonymous_variant	1/1	ENST00000620793.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8655 AN: 152118 Hom.: 364 Cov.: 33

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

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.: 37 AF XY: 0.0470 AC XY: 34139 AN XY: 725860

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.: 33 AF XY: 0.0568 AC XY: 4224 AN XY: 74424

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: criteria provided, single submitter

Submissions by phenotype

ADRA2B-related condition Benign:1

Benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs9333567; hg19: chr2-96781853; COSMIC: COSV69787444;