11-75284182-G-C

Variant names:

• chr11-75284182-G-C
• rs480174
• NM_004041.5:c.157+53C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004041.5(ARRB1):​c.157+53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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+53C>G		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.157+53C>G		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+53C>G		intron	N/A	ENSP00000409581.2
	ARRB1	ENST00000360025.7	TSL:1	c.157+53C>G		intron	N/A	ENSP00000353124.3
	ARRB1	ENST00000532525.1	TSL:5	c.142+53C>G		intron	N/A	ENSP00000433171.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.18e-7 AC: 1 AN: 1393094 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 689958

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31682

American (AMR) AF: 0.0000263 AC: 1 AN: 37998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23116

East Asian (EAS) AF: 0.00 AC: 0 AN: 38782

South Asian (SAS) AF: 0.00 AC: 0 AN: 78900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5342

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068662

Other (OTH) AF: 0.00 AC: 0 AN: 57112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.69
PhyloP100		-0.91

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: rs480174; hg19: chr11-74995226;