chr11-75284067-A-G

Variant names:

• chr11-75284067-A-G
• rs1320709
• NM_004041.5:c.157+168T>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.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
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 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.157+168T>C		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.157+168T>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.157+168T>C		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.157+168T>C		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000532525.1	TSL:5	c.142+168T>C		intron	N/A	ENSP00000433171.1

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

African (AFR) AF: 0.942 AC: 39110 AN: 41536

American (AMR) AF: 0.911 AC: 13946 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3014 AN: 3470

East Asian (EAS) AF: 0.811 AC: 4193 AN: 5172

South Asian (SAS) AF: 0.904 AC: 4357 AN: 4820

European-Finnish (FIN) AF: 0.963 AC: 10215 AN: 10606

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62697 AN: 68016

Other (OTH) AF: 0.927 AC: 1959 AN: 2114

Alfa AF: 0.918 Hom.: 32677

Bravo AF: 0.921

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.73
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1320709; hg19: chr11-74995111;