rs1042717

Positions:

• chr5-148827083-G-A
• chr5-148827083-G-C

Variant summary

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

The NM_000024.6(ADRB2):​c.252G>A​(p.Leu84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,613,882 control chromosomes in the GnomAD database, including 40,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5206 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35582 hom.)
• Consequence: ADRB2 NM_000024.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-148827083-G-A is Benign according to our data. Variant chr5-148827083-G-A is described in ClinVar as [Benign]. Clinvar id is 1225464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.076 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB2	NM_000024.6	c.252G>A	p.Leu84=	synonymous_variant	1/1	ENST00000305988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB2	ENST00000305988.6	c.252G>A	p.Leu84=	synonymous_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38092 AN: 152092 Hom.: 5203 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.257 AC: 64399 AN: 250862 Hom.: 9191 AF XY: 0.255 AC XY: 34598 AN XY: 135596

Gnomad AFR exome AF: 0.326

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.331

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.211 AC: 308624 AN: 1461670 Hom.: 35582 Cov.: 57 AF XY: 0.215 AC XY: 156149 AN XY: 727124

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.250 AC: 38116 AN: 152212 Hom.: 5206 Cov.: 33 AF XY: 0.251 AC XY: 18689 AN XY: 74428

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.263

Alfa AF: 0.209 Hom.: 8046

Bravo AF: 0.264

Asia WGS AF: 0.345 AC: 1198 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.218

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.7
DANN	Benign	0.89

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: rs1042717; hg19: chr5-148206646; COSMIC: COSV60005777;