NM_004313.4:c.23+500G>A

Variant names:

• chr17-4711244-G-A
• rs11868227
• NM_004313.4:c.23+500G>A

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+500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,836 control chromosomes in the GnomAD database, including 8,120 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 0.32 (8120 hom., cov: 30)
• Consequence: ARRB2 NM_004313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 6 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=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 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+500G>A		intron	N/A	NP_004304.1
	ARRB2	NM_001257328.2		c.23+500G>A		intron	N/A	NP_001244257.1
	ARRB2	NM_001257330.2		c.23+500G>A		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+500G>A		intron	N/A	ENSP00000269260.2
	ARRB2	ENST00000574954.5	TSL:1	c.-523+500G>A		intron	N/A	ENSP00000466344.1
	ARRB2	ENST00000412477.7	TSL:2	c.23+500G>A		intron	N/A	ENSP00000403701.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48294 AN: 151718 Hom.: 8102 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.318 AC: 48342 AN: 151836 Hom.: 8120 Cov.: 30 AF XY: 0.312 AC XY: 23170 AN XY: 74204

African (AFR) AF: 0.419 AC: 17347 AN: 41378

American (AMR) AF: 0.284 AC: 4327 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3468

East Asian (EAS) AF: 0.183 AC: 944 AN: 5150

South Asian (SAS) AF: 0.185 AC: 889 AN: 4804

European-Finnish (FIN) AF: 0.222 AC: 2346 AN: 10566

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20134 AN: 67912

Other (OTH) AF: 0.341 AC: 718 AN: 2104

Alfa AF: 0.304 Hom.: 910

Bravo AF: 0.330

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		0.15
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: rs11868227; hg19: chr17-4614539;