rs528833

Variant names:

• chr11-75269995-G-A
• rs528833
• NM_004041.5:c.1023-1036C>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.1023-1036C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,208 control chromosomes in the GnomAD database, including 10,297 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 0.33 (10297 hom., cov: 33)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 4 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 (AMR) allele frequency at 95% confidence interval = 0.436 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB1	NM_004041.5	MANE Select	c.1023-1036C>T		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.999-1036C>T		intron	N/A	NP_064647.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB1	ENST00000420843.7	TSL:1 MANE Select	c.1023-1036C>T		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.999-1036C>T		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000952726.1		c.1023-862C>T		intron	N/A	ENSP00000622785.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50409 AN: 152088 Hom.: 10299 Cov.: 33

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50418 AN: 152208 Hom.: 10297 Cov.: 33 AF XY: 0.335 AC XY: 24938 AN XY: 74388

African (AFR) AF: 0.0900 AC: 3742 AN: 41560

American (AMR) AF: 0.445 AC: 6805 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5174

South Asian (SAS) AF: 0.354 AC: 1711 AN: 4828

European-Finnish (FIN) AF: 0.474 AC: 5011 AN: 10568

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29611 AN: 67994

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.380 Hom.: 18484

Bravo AF: 0.319

Asia WGS AF: 0.283 AC: 984 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	2.8
DANN	Benign	0.45
PhyloP100		0.12
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: rs528833; hg19: chr11-74981039;