11-75288384-G-A

Variant names:

• chr11-75288384-G-A
• rs667791
• NM_004041.5:c.52-1009C>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.52-1009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,858 control chromosomes in the GnomAD database, including 24,621 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 0.56 (24621 hom., cov: 30)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 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.52-1009C>T		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.52-1009C>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.52-1009C>T		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.52-1009C>T		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000532525.1	TSL:5	c.37-1009C>T		intron	N/A	ENSP00000433171.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85733 AN: 151740 Hom.: 24626 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.565 AC: 85752 AN: 151858 Hom.: 24621 Cov.: 30 AF XY: 0.561 AC XY: 41641 AN XY: 74204

African (AFR) AF: 0.553 AC: 22898 AN: 41408

American (AMR) AF: 0.465 AC: 7104 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2091 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1914 AN: 5122

South Asian (SAS) AF: 0.561 AC: 2693 AN: 4804

European-Finnish (FIN) AF: 0.550 AC: 5800 AN: 10542

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41264 AN: 67930

Other (OTH) AF: 0.581 AC: 1226 AN: 2110

Alfa AF: 0.589 Hom.: 84325

Bravo AF: 0.554

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.033
DANN	Benign	0.61
PhyloP100		-1.5
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: rs667791; hg19: chr11-74999428;