dbSNP rs28763957: ADRB2:c.*26C>A (chr5-148828099-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000024.6(ADRB2):c.*26C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,280,378 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00041 ( 6 hom. )

Consequence

ADRB2
NM_000024.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

2 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.*26C>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADRB2	ENST00000305988.6 link	c.*26C>A	3_prime_UTR_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4	P07550
ENSG00000303969	ENST00000798472.1 link	n.376+2802C>A	intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1 link	n.349+2802C>A	intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

98850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000360

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000431

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000406

AC:

AN:

135490

AF XY:

0.000354

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000239

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000128

Gnomad NFE exome

AF:

0.000671

Gnomad OTH exome

AF:

0.000862

GnomAD4 exome

AF:

0.000415

AC:

490

AN:

1181528

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

229

AN XY:

592428

show subpopulations

African (AFR)

AF:

0.000105

AC:

AN:

28442

American (AMR)

AF:

0.00

AC:

AN:

32608

Ashkenazi Jewish (ASJ)

AF:

0.000246

AC:

AN:

20358

East Asian (EAS)

AF:

0.00

AC:

AN:

37870

South Asian (SAS)

AF:

0.00

AC:

AN:

70870

European-Finnish (FIN)

AF:

0.0000998

AC:

AN:

50116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.000493

AC:

437

AN:

885684

Other (OTH)

AF:

0.000790

AC:

AN:

50632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.646

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000283

AC:

AN:

98850

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

AN XY:

47312

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

15900

American (AMR)

AF:

0.00

AC:

AN:

9952

Ashkenazi Jewish (ASJ)

AF:

0.000360

AC:

AN:

2780

East Asian (EAS)

AF:

0.00

AC:

AN:

2336

South Asian (SAS)

AF:

0.00

AC:

AN:

2276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000431

AC:

AN:

55634

Other (OTH)

AF:

0.00

AC:

AN:

1416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.3

(source)

DANN

Benign

0.58

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over