Menu
GeneBe

rs1042713

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 14150 hom., cov: 35)
Exomes 𝑓: 0.38 ( 109675 hom. )

Consequence

ADRB2
NM_000024.6 missense

Scores

1
17

Clinical Significance

drug response reviewed by expert panel O:1

Conservation

PhyloP100: 1.81
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
ADRB2NM_000024.6 linkuse as main transcriptc.46G>A p.Gly16Arg missense_variant 1/1 ENST00000305988.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADRB2ENST00000305988.6 linkuse as main transcriptc.46G>A p.Gly16Arg missense_variant 1/1 NM_000024.6 P1

Frequencies

GnomAD3 genomes
AF:
0.426
AC:
64762
AN:
152090
Hom.:
14124
Cov.:
35
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
GnomAD3 exomes
AF:
0.421
AC:
105701
AN:
251152
Hom.:
22853
AF XY:
0.418
AC XY:
56692
AN XY:
135786
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 SAS exome
AF:
0.452
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.:
69
AF XY:
0.385
AC XY:
280174
AN XY:
726918
show subpopulations
Gnomad4 AFR exome
AF:
0.494
Gnomad4 AMR exome
AF:
0.431
Gnomad4 ASJ exome
AF:
0.442
Gnomad4 EAS exome
AF:
0.525
Gnomad4 SAS exome
AF:
0.449
Gnomad4 FIN exome
AF:
0.429
Gnomad4 NFE exome
AF:
0.365
Gnomad4 OTH exome
AF:
0.399
GnomAD4 genome
AF:
0.426
AC:
64831
AN:
152208
Hom.:
14150
Cov.:
35
AF XY:
0.431
AC XY:
32097
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.493
Gnomad4 AMR
AF:
0.435
Gnomad4 ASJ
AF:
0.430
Gnomad4 EAS
AF:
0.544
Gnomad4 SAS
AF:
0.444
Gnomad4 FIN
AF:
0.445
Gnomad4 NFE
AF:
0.372
Gnomad4 OTH
AF:
0.428
Alfa
AF:
0.388
Hom.:
28828
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
drug response, reviewed by expert panelcurationPharmGKBMar 24, 2021PharmGKB 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
T
BayesDel_noAF
Benign
-0.34
Cadd
Benign
18
Dann
Uncertain
0.98
DEOGEN2
Benign
0.080
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.79
T
MetaRNN
Benign
0.00013
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.90
L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.36
N
REVEL
Benign
0.079
Sift
Benign
0.35
T
Sift4G
Benign
0.50
T
Polyphen
0.043
B
Vest4
0.043
MutPred
0.33
Gain of catalytic residue at G16 (P = 0.0533);
MPC
0.74
ClinPred
0.0071
T
GERP RS
3.7
Varity_R
0.097
gMVP
0.62

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.

Other links and lift over

dbSNP: rs1042713; hg19: chr5-148206440; COSMIC: COSV60005269; API