dbSNP rs7099478: GRK5:c.738+147C>A (chr10-119431674-C-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_005308.3(GRK5):c.738+147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 942,410 control chromosomes in the GnomAD database, including 135,137 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 0.57 ( 25872 hom., cov: 33)

Exomes 𝑓: 0.52 ( 109265 hom. )

Consequence

GRK5
NM_005308.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

5 publications found

Variant links:

Genes affected

GRK5 (HGNC:4544): (G protein-coupled receptor kinase 5) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

GRK5 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK5	NM_005308.3 link	c.738+147C>A		intron_variant	Intron 8 of 15	ENST00000392870.3	NP_005299.1	P34947

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3 link	c.738+147C>A		intron_variant	Intron 8 of 15	1	NM_005308.3	ENSP00000376609.2		P34947

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87365

AN:

152044

Hom.:

25831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.543

GnomAD4 exome

AF:

0.517

AC:

408853

AN:

790248

Hom.:

109265

AF XY:

0.516

AC XY:

205200

AN XY:

397818

show subpopulations

African (AFR)

AF:

0.677

AC:

12019

AN:

17750

American (AMR)

AF:

0.673

AC:

12189

AN:

18112

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

8453

AN:

15498

East Asian (EAS)

AF:

0.324

AC:

9872

AN:

30446

South Asian (SAS)

AF:

0.451

AC:

22767

AN:

50460

European-Finnish (FIN)

AF:

0.591

AC:

21003

AN:

35514

Middle Eastern (MID)

AF:

0.522

AC:

1363

AN:

2612

European-Non Finnish (NFE)

AF:

0.517

AC:

301455

AN:

582954

Other (OTH)

AF:

0.535

AC:

19732

AN:

36902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9185

18371

27556

36742

45927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7042

14084

21126

28168

35210

<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:

0.575

AC:

87461

AN:

152162

Hom.:

25872

Cov.:

AF XY:

0.575

AC XY:

42761

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.690

AC:

28638

AN:

41532

American (AMR)

AF:

0.631

AC:

9658

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1950

AN:

3468

East Asian (EAS)

AF:

0.320

AC:

1647

AN:

5154

South Asian (SAS)

AF:

0.448

AC:

2161

AN:

4824

European-Finnish (FIN)

AF:

0.595

AC:

6311

AN:

10604

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35221

AN:

67966

Other (OTH)

AF:

0.543

AC:

1147

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1934

3869

5803

7738

9672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.535

Hom.:

55522

Bravo

AF:

0.586

Asia WGS

AF:

0.455

AC:

1585

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

0.36

(source)

DANN

Benign

0.73

PhyloP100

-1.3

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