dbSNP rs1042719: ADRB2:p.Gly351Gly (chr5-148827884-G-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

59 publications found

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:

ENSG00000303969 (HGNC:):

ENSG00000303969 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	NM_000024.6	MANE Select	c.1053G>C	p.Gly351Gly	synonymous	Exon 1 of 1	NP_000015.2	X5DQM5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADRB2	ENST00000305988.6	TSL:6 MANE Select	c.1053G>C	p.Gly351Gly	synonymous	Exon 1 of 1	ENSP00000305372.4	P07550
ENSG00000303969	ENST00000798472.1		n.376+2587G>C		intron	N/A
ENSG00000303969	ENST00000798473.1		n.349+2587G>C		intron	N/A

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

GnomAD2 exomes

AF:

0.337

AC:

84643

AN:

251332

AF XY:

0.336

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 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

African (AFR)

AF:

0.353

AC:

11832

AN:

33476

American (AMR)

AF:

0.436

AC:

19491

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7768

AN:

26134

East Asian (EAS)

AF:

0.482

AC:

19150

AN:

39696

South Asian (SAS)

AF:

0.390

AC:

33676

AN:

86256

European-Finnish (FIN)

AF:

0.258

AC:

13807

AN:

53418

Middle Eastern (MID)

AF:

0.370

AC:

2135

AN:

5768

European-Non Finnish (NFE)

AF:

0.279

AC:

310173

AN:

1111930

Other (OTH)

AF:

0.310

AC:

18728

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18779

37557

56336

75114

93893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10576

21152

31728

42304

52880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48780

AN:

151998

Hom.:

8075

Cov.:

AF XY:

0.321

AC XY:

23877

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.348

AC:

14432

AN:

41430

American (AMR)

AF:

0.382

AC:

5831

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

959

AN:

3464

East Asian (EAS)

AF:

0.452

AC:

2336

AN:

5166

South Asian (SAS)

AF:

0.400

AC:

1927

AN:

4816

European-Finnish (FIN)

AF:

0.268

AC:

2826

AN:

10556

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19305

AN:

67972

Other (OTH)

AF:

0.335

AC:

707

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1683

3366

5048

6731

8414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

(source)

DANN

Benign

0.80

PhyloP100

0.96

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over