rs3813662

chr2-96113947-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000682.7(ADRA2B):c.*850T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 985,830 control chromosomes in the GnomAD database, including 448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.029 (310 hom., cov: 33)
  • Exomes 𝑓: 0.012 (138 hom.)
• Consequence: ADRA2B NM_000682.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA2B	NM_000682.7	c.*850T>G		3_prime_UTR_variant	1/1	ENST00000620793.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA2B	ENST00000620793.2	c.*850T>G		3_prime_UTR_variant	1/1		NM_000682.7	P1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4452 AN: 152184 Hom.: 307 Cov.: 33

Gnomad AFR AF: 0.00514

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0401

GnomAD4 exome AF: 0.0117 AC: 9722 AN: 833526 Hom.: 138 Cov.: 27 AF XY: 0.0118 AC XY: 4539 AN XY: 384970

Gnomad4 AFR exome AF: 0.00469

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0537

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00955

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0293 AC: 4468 AN: 152304 Hom.: 310 Cov.: 33 AF XY: 0.0316 AC XY: 2350 AN XY: 74482

Gnomad4 AFR AF: 0.00512

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0275 Hom.: 247

Bravo AF: 0.0457

Asia WGS AF: 0.0810 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3813662; hg19: chr2-96779695; COSMIC: COSV69787428;