Genetic Variant 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:

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	NM_005308.3	MANE Select	c.738+147C>A		intron	N/A	NP_005299.1	P34947

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRK5	ENST00000392870.3	TSL:1 MANE Select	c.738+147C>A	intron	N/A	ENSP00000376609.2	P34947
GRK5	ENST00000857196.1		c.738+147C>A	intron	N/A	ENSP00000527255.1
GRK5	ENST00000857197.1		c.738+147C>A	intron	N/A	ENSP00000527256.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over