dbSNP rs480174: ARRB1:c.157+53C>T (chr11-75284182-G-A) – 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.157+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,543,834 control chromosomes in the GnomAD database, including 35,801 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 0.22 ( 3869 hom., cov: 31)

Exomes 𝑓: 0.21 ( 31932 hom. )

Consequence

ARRB1
NM_004041.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.911

Publications

6 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB1	NM_004041.5 link	c.157+53C>T		intron_variant	Intron 4 of 15	ENST00000420843.7	NP_004032.2	P49407-1B7Z1Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7 link	c.157+53C>T		intron_variant	Intron 4 of 15	1	NM_004041.5	ENSP00000409581.2		P49407-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33937

AN:

151824

Hom.:

3866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.212

AC:

295135

AN:

1391890

Hom.:

31932

AF XY:

0.211

AC XY:

145373

AN XY:

689296

show subpopulations

African (AFR)

AF:

0.230

AC:

7277

AN:

31656

American (AMR)

AF:

0.201

AC:

7634

AN:

37952

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

4542

AN:

23082

East Asian (EAS)

AF:

0.319

AC:

12373

AN:

38734

South Asian (SAS)

AF:

0.176

AC:

13892

AN:

78790

European-Finnish (FIN)

AF:

0.280

AC:

14394

AN:

51472

Middle Eastern (MID)

AF:

0.203

AC:

1084

AN:

5334

European-Non Finnish (NFE)

AF:

0.208

AC:

221745

AN:

1067802

Other (OTH)

AF:

0.214

AC:

12194

AN:

57068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

11360

22720

34079

45439

56799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7970

15940

23910

31880

39850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.224

AC:

33968

AN:

151944

Hom.:

3869

Cov.:

AF XY:

0.225

AC XY:

16720

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.233

AC:

9660

AN:

41430

American (AMR)

AF:

0.200

AC:

3059

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3470

East Asian (EAS)

AF:

0.339

AC:

1742

AN:

5146

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4810

European-Finnish (FIN)

AF:

0.291

AC:

3079

AN:

10574

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14175

AN:

67934

Other (OTH)

AF:

0.207

AC:

435

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1344

2688

4031

5375

6719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.197

Hom.:

2307

Bravo

AF:

0.221

Asia WGS

AF:

0.218

AC:

759

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.60

(source)

DANN

Benign

0.71

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over