chr11-75313772-T-G

Variant names:

• chr11-75313772-T-G
• rs508435
• NM_004041.5:c.21-23733A>C

Variant summary

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

The NM_004041.5(ARRB1):​c.21-23733A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,032 control chromosomes in the GnomAD database, including 29,826 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 0.62 (29826 hom., cov: 32)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 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.21-23733A>C		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.21-23733A>C		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.21-23733A>C		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.21-23733A>C		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000533255.1	TSL:2	n.74-23733A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93853 AN: 151914 Hom.: 29785 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.618 AC: 93953 AN: 152032 Hom.: 29826 Cov.: 32 AF XY: 0.613 AC XY: 45537 AN XY: 74316

African (AFR) AF: 0.775 AC: 32146 AN: 41480

American (AMR) AF: 0.554 AC: 8454 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2128 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3588 AN: 5156

South Asian (SAS) AF: 0.622 AC: 3000 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4754 AN: 10568

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38082 AN: 67954

Other (OTH) AF: 0.617 AC: 1303 AN: 2112

Alfa AF: 0.584 Hom.: 15768

Bravo AF: 0.630

Asia WGS AF: 0.655 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.58
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: rs508435; hg19: chr11-75024816;