Variant chr5-148827083-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0760

Variant links:

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]

ADRB2 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.215

AC XY:

156149

AN XY:

727124

show subpopulations

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.:

AF XY:

0.251

AC XY:

18689

AN XY:

74428

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over