chr11-75284182-G-A

Variant names:

• chr11-75284182-G-A
• rs480174
• NM_004041.5:c.157+53C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004041.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB1	NM_004041.5	MANE Select	c.157+53C>T		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.157+53C>T		intron	N/A	NP_064647.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB1	ENST00000420843.7	TSL:1 MANE Select	c.157+53C>T		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.157+53C>T		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000532525.1	TSL:5	c.142+53C>T		intron	N/A	ENSP00000433171.1

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

African (AFR) AF: 0.230 AC: 7277 AN: 31656

American (AMR) AF: 0.201 AC: 7634 AN: 37952

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 4542 AN: 23082

East Asian (EAS) AF: 0.319 AC: 12373 AN: 38734

South Asian (SAS) AF: 0.176 AC: 13892 AN: 78790

European-Finnish (FIN) AF: 0.280 AC: 14394 AN: 51472

Middle Eastern (MID) AF: 0.203 AC: 1084 AN: 5334

European-Non Finnish (NFE) AF: 0.208 AC: 221745 AN: 1067802

Other (OTH) AF: 0.214 AC: 12194 AN: 57068

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

African (AFR) AF: 0.233 AC: 9660 AN: 41430

American (AMR) AF: 0.200 AC: 3059 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1742 AN: 5146

South Asian (SAS) AF: 0.177 AC: 852 AN: 4810

European-Finnish (FIN) AF: 0.291 AC: 3079 AN: 10574

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14175 AN: 67934

Other (OTH) AF: 0.207 AC: 435 AN: 2104

Alfa AF: 0.197 Hom.: 2307

Bravo AF: 0.221

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.71
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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