chr17-4719585-A-G

Position:

• chr17-4719585-A-G

Variant summary

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

The NM_004313.4(ARRB2):​c.917+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,926 control chromosomes in the GnomAD database, including 31,587 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 0.63 (31587 hom., cov: 31)
• Consequence: ARRB2 NM_004313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

Genes affected

ARRB2 (HGNC:712): (arrestin beta 2) 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 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRB2	NM_004313.4	c.917+165A>G		intron_variant		ENST00000269260.7	NP_004304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRB2	ENST00000269260.7	c.917+165A>G		intron_variant		1	NM_004313.4	ENSP00000269260	P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96160 AN: 151808 Hom.: 31557 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.633 AC: 96227 AN: 151926 Hom.: 31587 Cov.: 31 AF XY: 0.641 AC XY: 47586 AN XY: 74268

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.626

Alfa AF: 0.630 Hom.: 5077

Bravo AF: 0.618

Asia WGS AF: 0.799 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2271167; hg19: chr17-4622880;