dbSNP rs3730109: GRK3:c.747+124A>G (chr22-25679039-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005160.4(GRK3):c.747+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 589,346 control chromosomes in the GnomAD database, including 3,774 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 0.11 ( 2911 hom., cov: 33)

Exomes 𝑓: 0.014 ( 863 hom. )

Consequence

GRK3
NM_005160.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.558

Publications

0 publications found

Variant links:

Genes affected

GRK3 (HGNC:290): (G protein-coupled receptor kinase 3) The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]

GRK3 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3	NM_005160.4 link	c.747+124A>G		intron_variant	Intron 9 of 20	ENST00000324198.11	NP_005151.2	P35626A0A024R1D8Q8N433

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11 link	c.747+124A>G		intron_variant	Intron 9 of 20	1	NM_005160.4	ENSP00000317578.4		P35626
GRK3	ENST00000455558.2 link	n.*469+124A>G		intron_variant	Intron 8 of 8	5		ENSP00000393688.2		H7C099

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16604

AN:

152058

Hom.:

2903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0522

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.0809

GnomAD4 exome

AF:

0.0139

AC:

6078

AN:

437172

Hom.:

863

AF XY:

0.0119

AC XY:

2748

AN XY:

230640

show subpopulations

African (AFR)

AF:

0.377

AC:

4009

AN:

10640

American (AMR)

AF:

0.0333

AC:

458

AN:

13772

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

143

AN:

12138

East Asian (EAS)

AF:

0.000149

AC:

AN:

26800

South Asian (SAS)

AF:

0.00443

AC:

158

AN:

35674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40260

Middle Eastern (MID)

AF:

0.0288

AC:

AN:

3302

European-Non Finnish (NFE)

AF:

0.00138

AC:

372

AN:

270538

Other (OTH)

AF:

0.0349

AC:

839

AN:

24048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

208

417

625

834

1042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.109

AC:

16649

AN:

152174

Hom.:

2911

Cov.:

AF XY:

0.106

AC XY:

7872

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.373

AC:

15461

AN:

41494

American (AMR)

AF:

0.0520

AC:

795

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00581

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00204

AC:

139

AN:

68000

Other (OTH)

AF:

0.0805

AC:

170

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

557

1115

1672

2230

2787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0963

Hom.:

281

Bravo

AF:

0.125

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.85

(source)

DANN

Benign

0.51

PhyloP100

-0.56

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