rs17133858

Positions:

• chr11-75260513-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.*5650C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,232 control chromosomes in the GnomAD database, including 495 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 0.062 (495 hom., cov: 31)
  • Exomes 𝑓: 0.047 (0 hom.)
• Consequence: ARRB1 NM_004041.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARRB1	NM_004041.5	c.*5650C>A		3_prime_UTR_variant	16/16	ENST00000420843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARRB1	ENST00000420843.7	c.*5650C>A		3_prime_UTR_variant	16/16	1	NM_004041.5	P1
	ENST00000624624.1	n.1954C>A		non_coding_transcript_exon_variant	1/1
	ENST00000529215.1	n.236+151G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9356 AN: 152050 Hom.: 494 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0469 AC: 3 AN: 64 Hom.: 0 Cov.: 0 AF XY: 0.0417 AC XY: 2 AN XY: 48

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0616 AC: 9373 AN: 152168 Hom.: 495 Cov.: 31 AF XY: 0.0619 AC XY: 4605 AN XY: 74394

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00714

Gnomad4 SAS AF: 0.0177

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0335 Hom.: 143

Bravo AF: 0.0642

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17133858; hg19: chr11-74971557;