rs480174

Positions:

• chr11-75284182-G-A
• chr11-75284182-G-C
• chr11-75284182-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004041.5(ARRB1):​c.157+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,543,834 control chromosomes in the GnomAD database, including 35,801 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 0.22 (3869 hom., cov: 31)
  • Exomes 𝑓: 0.21 (31932 hom.)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

Genes affected

ARRB1 (HGNC:711): (arrestin beta 1) 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 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRB1	NM_004041.5	c.157+53C>T		intron_variant		ENST00000420843.7	NP_004032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7	c.157+53C>T		intron_variant		1	NM_004041.5	ENSP00000409581.2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33937 AN: 151824 Hom.: 3866 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.212 AC: 295135 AN: 1391890 Hom.: 31932 AF XY: 0.211 AC XY: 145373 AN XY: 689296

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.224 AC: 33968 AN: 151944 Hom.: 3869 Cov.: 31 AF XY: 0.225 AC XY: 16720 AN XY: 74248

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.207

Alfa AF: 0.192 Hom.: 1645

Bravo AF: 0.221

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs480174; hg19: chr11-74995226; COSMIC: COSV63574553; COSMIC: COSV63574553;