17-4717202-C-T

Position:

• chr17-4717202-C-T

Variant summary

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

The NM_004313.4(ARRB2):​c.358-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,613,470 control chromosomes in the GnomAD database, including 702,728 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 0.91 (63213 hom., cov: 31)
  • Exomes 𝑓: 0.94 (639515 hom.)
• Consequence: ARRB2 NM_004313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613

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]

ARRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRB2	NM_004313.4	c.358-15C>T		intron_variant		ENST00000269260.7	NP_004304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRB2	ENST00000269260.7	c.358-15C>T		intron_variant		1	NM_004313.4	ENSP00000269260.2

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138397 AN: 152070 Hom.: 63174 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.900

GnomAD3 exomes AF: 0.938 AC: 235678 AN: 251322 Hom.: 110651 AF XY: 0.939 AC XY: 127528 AN XY: 135844

Gnomad AFR exome AF: 0.831

Gnomad AMR exome AF: 0.956

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.952

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.922

GnomAD4 exome AF: 0.935 AC: 1366642 AN: 1461282 Hom.: 639515 Cov.: 42 AF XY: 0.936 AC XY: 680464 AN XY: 726972

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.884

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.951

Gnomad4 FIN exome AF: 0.951

Gnomad4 NFE exome AF: 0.935

Gnomad4 OTH exome AF: 0.923

GnomAD4 genome AF: 0.910 AC: 138491 AN: 152188 Hom.: 63213 Cov.: 31 AF XY: 0.911 AC XY: 67792 AN XY: 74394

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.901

Alfa AF: 0.916 Hom.: 13131

Bravo AF: 0.905

Asia WGS AF: 0.959 AC: 3337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.59

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: rs7208257; hg19: chr17-4620497;