11-75284067-A-G

Variant names:

• chr11-75284067-A-G
• rs1320709
• NM_004041.5:c.157+168T>C

Variant summary

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

The NM_004041.5(ARRB1):​c.157+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,250 control chromosomes in the GnomAD database, including 65,068 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 0.92 (65068 hom., cov: 32)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB1	NM_004041.5	c.157+168T>C		intron_variant	Intron 4 of 15	ENST00000420843.7	NP_004032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7	c.157+168T>C		intron_variant	Intron 4 of 15	1	NM_004041.5	ENSP00000409581.2

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140555 AN: 152132 Hom.: 65028 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.924 AC: 140653 AN: 152250 Hom.: 65068 Cov.: 32 AF XY: 0.925 AC XY: 68844 AN XY: 74430

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.927

Alfa AF: 0.918 Hom.: 29068

Bravo AF: 0.921

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1320709; hg19: chr11-74995111;