11-75310457-C-T

Position:

• chr11-75310457-C-T

Variant summary

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

The NM_004041.5(ARRB1):​c.21-20418G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,016 control chromosomes in the GnomAD database, including 28,056 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 0.60 (28056 hom., cov: 32)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARRB1	NM_004041.5	c.21-20418G>A		intron_variant		ENST00000420843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARRB1	ENST00000420843.7	c.21-20418G>A		intron_variant		1	NM_004041.5	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90803 AN: 151898 Hom.: 28029 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.598 AC: 90890 AN: 152016 Hom.: 28056 Cov.: 32 AF XY: 0.593 AC XY: 44031 AN XY: 74296

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.592

Alfa AF: 0.548 Hom.: 45985

Bravo AF: 0.612

Asia WGS AF: 0.642 AC: 2235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.77

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: rs472112; hg19: chr11-75021501; COSMIC: COSV63575802; COSMIC: COSV63575802;