Variant 5-148827884-G-C 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.1053G>C(p.Gly351Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,613,788 control chromosomes in the GnomAD database, including 75,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8075 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67444 hom. )

Consequence

ADRB2
NM_000024.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.960

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:

Genome browser will be placed here

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 5-148827884-G-C is Benign according to our data. Variant chr5-148827884-G-C is described in ClinVar as [Benign]. Clinvar id is 1236780.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.1053G>C	p.Gly351Gly	synonymous_variant	1/1	ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988.6 link	c.1053G>C	p.Gly351Gly	synonymous_variant	1/1	6	NM_000024.6	ENSP00000305372.4		P07550

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48756

AN:

151880

Hom.:

8074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.337

AC:

84643

AN:

251332

Hom.:

15011

AF XY:

0.336

AC XY:

45671

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.443

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.446

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.299

AC:

436760

AN:

1461790

Hom.:

67444

Cov.:

AF XY:

0.302

AC XY:

219398

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.321

AC:

48780

AN:

151998

Hom.:

8075

Cov.:

AF XY:

0.321

AC XY:

23877

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.277

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.296

Hom.:

2335

Bravo

AF:

0.329

Asia WGS

AF:

0.417

AC:

1450

AN:

3478

EpiCase

AF:

0.293

EpiControl

AF:

0.302

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

7.6

DANN

Benign

0.80

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