17-4710335-C-T

Variant names:

• chr17-4710335-C-T
• rs34230287
• ENST00000855436.1:c.-387C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000855436.1(ARRB2):​c.-387C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,170 control chromosomes in the GnomAD database, including 2,487 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 0.16 (2487 hom., cov: 32)
• Consequence: ARRB2 ENST00000855436.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000855436.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB2	ENST00000855436.1		c.-387C>T		upstream_gene	N/A	ENSP00000525496.1
	ARRB2	ENST00000915218.1		c.-387C>T		upstream_gene	N/A	ENSP00000585277.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24006 AN: 152052 Hom.: 2490 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.158 AC: 23992 AN: 152170 Hom.: 2487 Cov.: 32 AF XY: 0.153 AC XY: 11363 AN XY: 74410

African (AFR) AF: 0.0428 AC: 1778 AN: 41560

American (AMR) AF: 0.150 AC: 2297 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5172

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10604

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16226 AN: 67954

Other (OTH) AF: 0.172 AC: 363 AN: 2110

Alfa AF: 0.199 Hom.: 5573

Bravo AF: 0.149

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		-0.16
PromoterAI		0.0060	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34230287;

hg19: chr17-4613630;