dbSNP rs4522461: ARRB2:c.706+133T>G (chr17-4718478-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004313.4(ARRB2):c.706+133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,245,738 control chromosomes in the GnomAD database, including 398,394 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 0.82 ( 51450 hom., cov: 30)

Exomes 𝑓: 0.79 ( 346944 hom. )

Consequence

ARRB2
NM_004313.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.760

Publications

16 publications found

Variant links:

Genes affected

ARRB2 (HGNC:712): (arrestin beta 2) Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

ARRB2 links:

ENSG00000302420 (HGNC:):

ENSG00000302420 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB2	NM_004313.4 link	c.706+133T>G		intron_variant	Intron 9 of 14	ENST00000269260.7	NP_004304.1	P32121-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRB2	ENST00000269260.7 link	c.706+133T>G		intron_variant	Intron 9 of 14	1	NM_004313.4	ENSP00000269260.2		P32121-1

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

124582

AN:

151902

Hom.:

51384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.840

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.910

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.761

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.811

GnomAD4 exome

AF:

0.793

AC:

867839

AN:

1093718

Hom.:

346944

Cov.:

AF XY:

0.796

AC XY:

442926

AN XY:

556462

show subpopulations

African (AFR)

AF:

0.894

AC:

23253

AN:

26018

American (AMR)

AF:

0.889

AC:

36378

AN:

40934

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

18017

AN:

21510

East Asian (EAS)

AF:

1.00

AC:

37955

AN:

37970

South Asian (SAS)

AF:

0.891

AC:

66676

AN:

74844

European-Finnish (FIN)

AF:

0.814

AC:

35499

AN:

43604

Middle Eastern (MID)

AF:

0.822

AC:

3707

AN:

4510

European-Non Finnish (NFE)

AF:

0.763

AC:

607613

AN:

796224

Other (OTH)

AF:

0.805

AC:

38741

AN:

48104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9250

18499

27749

36998

46248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12876

25752

38628

51504

64380

<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:

0.820

AC:

124709

AN:

152020

Hom.:

51450

Cov.:

AF XY:

0.826

AC XY:

61381

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.883

AC:

36616

AN:

41458

American (AMR)

AF:

0.840

AC:

12833

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

2909

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5145

AN:

5154

South Asian (SAS)

AF:

0.911

AC:

4382

AN:

4812

European-Finnish (FIN)

AF:

0.821

AC:

8677

AN:

10574

Middle Eastern (MID)

AF:

0.764

AC:

223

AN:

292

European-Non Finnish (NFE)

AF:

0.760

AC:

51658

AN:

67968

Other (OTH)

AF:

0.813

AC:

1715

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1126

2251

3377

4502

5628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.807

Hom.:

39134

Bravo

AF:

0.826

Asia WGS

AF:

0.945

AC:

3284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.76

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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