rs16954146

chr17-4715177-G-Achr17-4715177-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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]

ACMG classification

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	UniProt
ARRB2	NM_004313.4	c.54+134G>A		intron_variant		ENST00000269260.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARRB2	ENST00000269260.7	c.54+134G>A		intron_variant		1	NM_004313.4	P1

Frequencies

GnomAD3 genomes AF: 0.0895 AC: 13598 AN: 151962 Hom.: 1467 Cov.: 30

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

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.: 11 AF XY: 0.0262 AC XY: 11773 AN XY: 449296

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.: 30 AF XY: 0.0891 AC XY: 6624 AN XY: 74330

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	16
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

Other links and lift over

dbSNP: rs16954146; hg19: chr17-4618472; COSMIC: COSV52616911; COSMIC: COSV52616911;