Variant chr17-4715177-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004313.4(ARRB2):c.54+134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,050,348 control chromosomes in the GnomAD database, including 2,861 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 0.090 ( 1473 hom., cov: 30)

Exomes 𝑓: 0.026 ( 1388 hom. )

Consequence

ARRB2
NM_004313.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

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:

ARRB2 (HGNC:):

ARRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRB2	NM_004313.4 linkuse as main transcript	c.54+134G>A		intron_variant		ENST00000269260.7	NP_004304.1	P32121-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRB2	ENST00000269260.7 linkuse as main transcript	c.54+134G>A		intron_variant		1	NM_004313.4	ENSP00000269260.2		P32121-1

Frequencies

GnomAD3 genomes

AF:

0.0895

AC:

13598

AN:

151962

Hom.:

1467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0650

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.0530

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0846

GnomAD3 exomes

AF:

0.0703

AC:

5547

AN:

78856

Hom.:

476

AF XY:

0.0666

AC XY:

2593

AN XY:

38952

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.0874

Gnomad ASJ exome

AF:

0.0521

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.0550

Gnomad FIN exome

AF:

0.00281

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0265

AC:

23775

AN:

898268

Hom.:

1388

Cov.:

AF XY:

0.0262

AC XY:

11773

AN XY:

449296

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.0431

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.0452

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.00994

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0896

AC:

13628

AN:

152080

Hom.:

1473

Cov.:

AF XY:

0.0891

AC XY:

6624

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.0649

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.0533

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.0837

Alfa

AF:

0.0489

Hom.:

173

Bravo

AF:

0.103

Asia WGS

AF:

0.103

AC:

359

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over