dbSNP rs17133858: ARRB1:c.*5650C>A (chr11-75260513-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004041.5(ARRB1):c.*5650C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,232 control chromosomes in the GnomAD database, including 495 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 0.062 ( 495 hom., cov: 31)

Exomes 𝑓: 0.047 ( 0 hom. )

Consequence

ARRB1
NM_004041.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.312

Publications

4 publications found

Variant links:

Genes affected

ARRB1 (HGNC:711): (arrestin beta 1) 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 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

ARRB1 links:

ENSG00000279117 (HGNC:):

ENSG00000279117 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB1	NM_004041.5 link	c.*5650C>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000420843.7	NP_004032.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ARRB1	ENST00000420843.7 link	c.*5650C>A	3_prime_UTR_variant	Exon 16 of 16	1	NM_004041.5	ENSP00000409581.2
ENSG00000279117	ENST00000624624.1 link	n.1954C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000254429	ENST00000529215.1 link	n.236+151G>T	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9356

AN:

152050

Hom.:

494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.00712

Gnomad SAS

AF:

0.0181

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0489

GnomAD4 exome

AF:

0.0469

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0417

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0536

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0616

AC:

9373

AN:

152168

Hom.:

495

Cov.:

AF XY:

0.0619

AC XY:

4605

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.144

AC:

5966

AN:

41470

American (AMR)

AF:

0.0306

AC:

468

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3470

East Asian (EAS)

AF:

0.00714

AC:

AN:

5184

South Asian (SAS)

AF:

0.0177

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.0566

AC:

600

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0283

AC:

1924

AN:

68016

Other (OTH)

AF:

0.0483

AC:

102

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

428

855

1283

1710

2138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0405

Hom.:

631

Bravo

AF:

0.0642

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.1

(source)

DANN

Benign

0.83

PhyloP100

0.31

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over