rs3729943

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000024.6(ADRB2):c.659C>G(p.Ser220Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,614,136 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

ADRB2
NM_000024.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

Publications

18 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012524247).

BP6

Variant 5-148827490-C-G is Benign according to our data. Variant chr5-148827490-C-G is described in ClinVar as Benign. ClinVar VariationId is 703951.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0072 (1097/152264) while in subpopulation AFR AF = 0.0252 (1046/41548). AF 95% confidence interval is 0.0239. There are 17 homozygotes in GnomAd4. There are 510 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1097 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.659C>G	p.Ser220Cys	missense_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ADRB2	ENST00000305988.6 link	c.659C>G	p.Ser220Cys	missense_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1 link	n.376+2193C>G		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1 link	n.349+2193C>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1092

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.00195

AC:

490

AN:

251480

AF XY:

0.00140

show subpopulations

Gnomad AFR exome

AF:

0.0260

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000781

AC:

1141

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000649

AC XY:

472

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0265

AC:

888

AN:

33480

American (AMR)

AF:

0.00116

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000139

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000719

AC:

AN:

1112006

Other (OTH)

AF:

0.00176

AC:

106

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00720

AC:

1097

AN:

152264

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0252

AC:

1046

AN:

41548

American (AMR)

AF:

0.00203

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000526

Hom.:

Bravo

AF:

0.00853

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00251

AC:

305

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.1

PhyloP100

1.2

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

REVEL

Benign

0.28

Sift

Uncertain

0.028

Sift4G

Benign

0.18

Vest4

0.36

ClinPred

0.022

GERP RS

5.6

Varity_R

0.63

gMVP

0.67

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over