NM_004313.4:c.23+1059A>G

Variant names:

• chr17-4711803-A-G
• rs3786047
• NM_004313.4:c.23+1059A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004313.4(ARRB2):​c.23+1059A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,030 control chromosomes in the GnomAD database, including 30,935 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 0.62 (30935 hom., cov: 32)
• Consequence: ARRB2 NM_004313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 34 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004313.4. 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
	ARRB2	NM_004313.4	MANE Select	c.23+1059A>G		intron	N/A	NP_004304.1
	ARRB2	NM_001257328.2		c.23+1059A>G		intron	N/A	NP_001244257.1
	ARRB2	NM_001257330.2		c.23+1059A>G		intron	N/A	NP_001244259.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB2	ENST00000269260.7	TSL:1 MANE Select	c.23+1059A>G		intron	N/A	ENSP00000269260.2
	ARRB2	ENST00000574954.5	TSL:1	c.-523+1059A>G		intron	N/A	ENSP00000466344.1
	ARRB2	ENST00000412477.7	TSL:2	c.23+1059A>G		intron	N/A	ENSP00000403701.3

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94670 AN: 151912 Hom.: 30909 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.623 AC: 94728 AN: 152030 Hom.: 30935 Cov.: 32 AF XY: 0.631 AC XY: 46880 AN XY: 74316

African (AFR) AF: 0.410 AC: 16992 AN: 41430

American (AMR) AF: 0.686 AC: 10470 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2360 AN: 3468

East Asian (EAS) AF: 0.817 AC: 4214 AN: 5158

South Asian (SAS) AF: 0.814 AC: 3925 AN: 4820

European-Finnish (FIN) AF: 0.767 AC: 8128 AN: 10602

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46710 AN: 67962

Other (OTH) AF: 0.619 AC: 1309 AN: 2114

Alfa AF: 0.649 Hom.: 34913

Bravo AF: 0.606

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs3786047; hg19: chr17-4615098;