rs28763957

chr5-148828099-C-Achr5-148828099-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000024.6(ADRB2):c.*26C>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 0.000405 in 1,280,378 control chromosomes in the GnomAD database, including 6 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 0.00028 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: ADRB2 NM_000024.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

ADRB2 (HGNC:286): (adrenoceptor beta 2) This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB2	NM_000024.6	c.*26C>A		3_prime_UTR_variant	1/1	ENST00000305988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB2	ENST00000305988.6	c.*26C>A		3_prime_UTR_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 28 AN: 98850 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000431

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000406 AC: 55 AN: 135490 Hom.: 0 AF XY: 0.000354 AC XY: 26 AN XY: 73356

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000239

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000128

Gnomad NFE exome AF: 0.000671

Gnomad OTH exome AF: 0.000862

GnomAD4 exome AF: 0.000415 AC: 490 AN: 1181528 Hom.: 6 Cov.: 25 AF XY: 0.000387 AC XY: 229 AN XY: 592428

Gnomad4 AFR exome AF: 0.000105

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000246

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000998

Gnomad4 NFE exome AF: 0.000493

Gnomad4 OTH exome AF: 0.000790

GnomAD4 genome AF: 0.000283 AC: 28 AN: 98850 Hom.: 0 Cov.: 27 AF XY: 0.000380 AC XY: 18 AN XY: 47312

Gnomad4 AFR AF: 0.000189

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000360

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000431

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.3
Dann	Benign	0.58

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: rs28763957; hg19: chr5-148207662;