rs11868227

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARRB2NM_004313.4 linkuse as main transcriptc.23+500G>A intron_variant ENST00000269260.7 NP_004304.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARRB2ENST00000269260.7 linkuse as main transcriptc.23+500G>A intron_variant 1 NM_004313.4 ENSP00000269260 P1P32121-1

Frequencies

GnomAD3 genomes
AF:
0.318
AC:
48294
AN:
151718
Hom.:
8102
Cov.:
30
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.419
Gnomad4 AMR
AF:
0.284
Gnomad4 ASJ
AF:
0.306
Gnomad4 EAS
AF:
0.183
Gnomad4 SAS
AF:
0.185
Gnomad4 FIN
AF:
0.222
Gnomad4 NFE
AF:
0.296
Gnomad4 OTH
AF:
0.341
Alfa
AF:
0.299
Hom.:
839
Bravo
AF:
0.330
Asia WGS
AF:
0.191
AC:
664
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
16
DANN
Benign
0.87

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11868227; hg19: chr17-4614539; API