rs1042713

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000024.6(ADRB2):c.46G>A(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,480 control chromosomes in the GnomAD database, including 123,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

Frequency

Genomes: 𝑓 0.43 ( 14150 hom., cov: 35)

Exomes 𝑓: 0.38 ( 109675 hom. )

Consequence

ADRB2
NM_000024.6 missense

Scores

Clinical Significance

drug response reviewed by expert panel O:1

Conservation

PhyloP100: 1.81

Publications

1013 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3175607E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.46G>A	p.Gly16Arg	missense_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADRB2	ENST00000305988.6 link	c.46G>A	p.Gly16Arg	missense_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4	P07550
ENSG00000303969	ENST00000798472.1 link	n.376+1580G>A		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1 link	n.349+1580G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64762

AN:

152090

Hom.:

14124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.421

GnomAD2 exomes

AF:

0.421

AC:

105701

AN:

251152

AF XY:

0.418

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.384

AC:

561623

AN:

1461272

Hom.:

109675

Cov.:

AF XY:

0.385

AC XY:

280174

AN XY:

726918

show subpopulations

African (AFR)

AF:

0.494

AC:

16521

AN:

33468

American (AMR)

AF:

0.431

AC:

19294

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

11542

AN:

26134

East Asian (EAS)

AF:

0.525

AC:

20860

AN:

39700

South Asian (SAS)

AF:

0.449

AC:

38673

AN:

86220

European-Finnish (FIN)

AF:

0.429

AC:

22885

AN:

53370

Middle Eastern (MID)

AF:

0.400

AC:

2154

AN:

5380

European-Non Finnish (NFE)

AF:

0.365

AC:

405627

AN:

1111944

Other (OTH)

AF:

0.399

AC:

24067

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

20632

41264

61896

82528

103160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13090

26180

39270

52360

65450

<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:

0.426

AC:

64831

AN:

152208

Hom.:

14150

Cov.:

AF XY:

0.431

AC XY:

32097

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.493

AC:

20499

AN:

41542

American (AMR)

AF:

0.435

AC:

6658

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1492

AN:

3470

East Asian (EAS)

AF:

0.544

AC:

2805

AN:

5154

South Asian (SAS)

AF:

0.444

AC:

2143

AN:

4828

European-Finnish (FIN)

AF:

0.445

AC:

4712

AN:

10586

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.372

AC:

25312

AN:

68002

Other (OTH)

AF:

0.428

AC:

905

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1989

3977

5966

7954

9943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.391

Hom.:

57298

Bravo

AF:

0.427

TwinsUK

AF:

0.363

AC:

1345

ALSPAC

AF:

0.375

AC:

1446

ESP6500AA

AF:

0.487

AC:

2147

ESP6500EA

AF:

0.378

AC:

3249

ExAC

AF:

0.420

AC:

51023

Asia WGS

AF:

0.487

AC:

1689

AN:

3478

EpiCase

AF:

0.371

EpiControl

AF:

0.367

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

salmeterol response - Efficacy

Other:1

Mar 24, 2021

PharmGKB

Significance:drug response

Review Status:reviewed by expert panel

Collection Method:curation

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.080

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

MetaRNN

Benign

0.00013

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

1.8

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.36

REVEL

Benign

0.079

Sift

Benign

0.35

Sift4G

Benign

0.50

Polyphen

0.043

Vest4

0.043

MutPred

0.33

Gain of catalytic residue at G16 (P = 0.0533);

MPC

0.74

ClinPred

0.0071

GERP RS

3.7

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.097

gMVP

0.62

Mutation Taster

=95/5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over