chr5-148827322-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000024.6(ADRB2):c.491C>T(p.Thr164Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,614,130 control chromosomes in the GnomAD database, including 158 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 Benign (★). Synonymous variant affecting the same amino acid position (i.e. T164T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0090 ( 10 hom., cov: 33)

Exomes 𝑓: 0.012 ( 148 hom. )

Consequence

ADRB2
NM_000024.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 3.11

Publications

243 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0117586255).

BP6

Variant 5-148827322-C-T is Benign according to our data. Variant chr5-148827322-C-T is described in ClinVar as Benign. ClinVar VariationId is 17744.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1377 AD gene.

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.491C>T	p.Thr164Ile	missense	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.491C>T	p.Thr164Ile	missense	Exon 1 of 1	ENSP00000305372.4	P07550
ENSG00000303969	ENST00000798472.1		n.376+2025C>T		intron	N/A
ENSG00000303969	ENST00000798473.1		n.349+2025C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1378

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00907

AC:

2281

AN:

251490

AF XY:

0.00962

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00720

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0125

AC:

18200

AN:

1461822

Hom.:

148

Cov.:

AF XY:

0.0121

AC XY:

8778

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

33476

American (AMR)

AF:

0.00770

AC:

344

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00719

AC:

188

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00409

AC:

353

AN:

86254

European-Finnish (FIN)

AF:

0.00509

AC:

272

AN:

53414

Middle Eastern (MID)

AF:

0.0173

AC:

100

AN:

5768

European-Non Finnish (NFE)

AF:

0.0144

AC:

16066

AN:

1111986

Other (OTH)

AF:

0.0134

AC:

807

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1142

2284

3426

4568

5710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.00904

AC:

1377

AN:

152308

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00245

AC:

102

AN:

41568

American (AMR)

AF:

0.0134

AC:

205

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00352

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00330

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

956

AN:

68030

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

147

220

294

367

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:

0.0120

Hom.:

Bravo

AF:

0.00953

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0150

AC:

129

ExAC

AF:

0.00945

AC:

1148

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0136

EpiControl

AF:

0.0158

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Beta-2-adrenoreceptor agonist, reduced response to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.090

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.1

PhyloP100

3.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

2.1

REVEL

Benign

0.17

Sift

Benign

0.59

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MVP

0.60

MPC

0.57

ClinPred

0.027

GERP RS

5.7

Varity_R

0.57

gMVP

0.54

Mutation Taster

=28/72

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over