Genetic Variant 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:

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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=-0.81).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004041.5. 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
	ARRB1	NM_004041.5	MANE Select	c.*5650C>A		3_prime_UTR	Exon 16 of 16	NP_004032.2
	ARRB1	NM_020251.4		c.*5650C>A		3_prime_UTR	Exon 15 of 15	NP_064647.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARRB1	ENST00000420843.7	TSL:1 MANE Select	c.*5650C>A	3_prime_UTR	Exon 16 of 16	ENSP00000409581.2
ENSG00000279117	ENST00000624624.1	TSL:6	n.1954C>A	non_coding_transcript_exon	Exon 1 of 1
ENSG00000254429	ENST00000529215.1	TSL:2	n.236+151G>T	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over