NM_004041.5:c.21-12709G>A

Variant names:

• chr11-75302748-C-T
• rs11236388
• NM_004041.5:c.21-12709G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004041.5(ARRB1):​c.21-12709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,266 control chromosomes in the GnomAD database, including 327 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 0.055 (327 hom., cov: 32)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 3 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 = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB1	NM_004041.5	c.21-12709G>A		intron_variant	Intron 1 of 15	ENST00000420843.7	NP_004032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7	c.21-12709G>A		intron_variant	Intron 1 of 15	1	NM_004041.5	ENSP00000409581.2

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8421 AN: 152148 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0554 AC: 8437 AN: 152266 Hom.: 327 Cov.: 32 AF XY: 0.0538 AC XY: 4003 AN XY: 74444

African (AFR) AF: 0.0198 AC: 824 AN: 41552

American (AMR) AF: 0.0570 AC: 872 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.0568 AC: 294 AN: 5180

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4820

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5207 AN: 68018

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0709 Hom.: 306

Bravo AF: 0.0539

Asia WGS AF: 0.0750 AC: 260 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	0.17
DANN	Benign	0.21
PhyloP100		-1.4
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: rs11236388; hg19: chr11-75013792;