chr2-96114374-G-T

Position:

• chr2-96114374-G-T

Variant summary

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

The NM_000682.7(ADRA2B):​c.*423C>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 0.316 in 998,272 control chromosomes in the GnomAD database, including 50,897 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 0.32 (8318 hom., cov: 33)
  • Exomes 𝑓: 0.32 (42579 hom.)
• Consequence: ADRA2B NM_000682.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7	c.*423C>A		3_prime_UTR_variant	1/1	ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793	c.*423C>A		3_prime_UTR_variant	1/1		NM_000682.7	ENSP00000480573.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48412 AN: 151956 Hom.: 8299 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.315 AC: 266917 AN: 846198 Hom.: 42579 Cov.: 28 AF XY: 0.314 AC XY: 122875 AN XY: 391436

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.319 AC: 48482 AN: 152074 Hom.: 8318 Cov.: 33 AF XY: 0.325 AC XY: 24137 AN XY: 74338

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.276

Alfa AF: 0.282 Hom.: 3036

Bravo AF: 0.322

Asia WGS AF: 0.311 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4907299; hg19: chr2-96780122;