11-75313772-T-G

Position:

• chr11-75313772-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ARRB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRB1	NM_004041.5	c.21-23733A>C		intron_variant		ENST00000420843.7	NP_004032.2
ARRB1	NM_020251.4	c.21-23733A>C		intron_variant			NP_064647.1
ARRB1	XM_017017752.3	c.21-23733A>C		intron_variant			XP_016873241.1
ARRB1	XM_017017754.3	c.21-23733A>C		intron_variant			XP_016873243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7	c.21-23733A>C		intron_variant		1	NM_004041.5	ENSP00000409581.2
ARRB1	ENST00000360025.7	c.21-23733A>C		intron_variant		1		ENSP00000353124.3
ARRB1	ENST00000533255.1	n.74-23733A>C		intron_variant		2

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

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.617

Alfa AF: 0.586 Hom.: 14529

Bravo AF: 0.630

Asia WGS AF: 0.655 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.47

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: rs508435; hg19: chr11-75024816;