Variant 5-148827354-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_000024.6(ADRB2):c.523C>A(p.Arg175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,954 control chromosomes in the GnomAD database, including 32,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4561 hom., cov: 32)

Exomes 𝑓: 0.18 ( 28113 hom. )

Consequence

ADRB2
NM_000024.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.836

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 5-148827354-C-A is Benign according to our data. Variant chr5-148827354-C-A is described in ClinVar as [Benign]. Clinvar id is 1264227.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.836 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 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.523C>A	p.Arg175=	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.523C>A	p.Arg175=	synonymous_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34874

AN:

151988

Hom.:

4559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.232

AC:

58331

AN:

251470

Hom.:

7863

AF XY:

0.228

AC XY:

30955

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.185

AC:

269780

AN:

1461848

Hom.:

28113

Cov.:

AF XY:

0.187

AC XY:

136087

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.328

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.368

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.229

AC:

34901

AN:

152106

Hom.:

4561

Cov.:

AF XY:

0.229

AC XY:

17057

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.188

Hom.:

4784

Bravo

AF:

0.247

Asia WGS

AF:

0.333

AC:

1158

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.188

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

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.88

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