Genetic Variant GRK4:c.149-1818C>T (chr4-2986909-C-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_182982.3(GRK4):c.149-1818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 300,206 control chromosomes in the GnomAD database, including 26,715 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 0.45 ( 16421 hom., cov: 31)

Exomes 𝑓: 0.36 ( 10294 hom. )

Consequence

GRK4
NM_182982.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

13 publications found

Variant links:

Genes affected

GRK4 (HGNC:4543): (G protein-coupled receptor kinase 4) 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 its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GRK4 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182982.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRK4	NM_182982.3	MANE Select	c.149-1818C>T	intron	N/A	NP_892027.2	P32298-1
GRK4	NM_001004056.2		c.53-1818C>T	intron	N/A	NP_001004056.1	P32298-2
GRK4	NM_001004057.2		c.149-1818C>T	intron	N/A	NP_001004057.1	P32298-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRK4	ENST00000398052.9	TSL:1 MANE Select	c.149-1818C>T	intron	N/A	ENSP00000381129.4	P32298-1
GRK4	ENST00000345167.10	TSL:1	c.53-1818C>T	intron	N/A	ENSP00000264764.8	P32298-2
GRK4	ENST00000504933.1	TSL:1	c.149-1818C>T	intron	N/A	ENSP00000427445.1	P32298-4

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68420

AN:

151746

Hom.:

16394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.415

GnomAD4 exome

AF:

0.356

AC:

52820

AN:

148342

Hom.:

10294

AF XY:

0.339

AC XY:

28297

AN XY:

83552

show subpopulations

African (AFR)

AF:

0.599

AC:

2333

AN:

3894

American (AMR)

AF:

0.355

AC:

2310

AN:

6508

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1348

AN:

3666

East Asian (EAS)

AF:

0.173

AC:

1078

AN:

6216

South Asian (SAS)

AF:

0.221

AC:

6907

AN:

31320

European-Finnish (FIN)

AF:

0.504

AC:

3484

AN:

6908

Middle Eastern (MID)

AF:

0.419

AC:

823

AN:

1966

European-Non Finnish (NFE)

AF:

0.394

AC:

31875

AN:

80870

Other (OTH)

AF:

0.381

AC:

2662

AN:

6994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1482

2963

4445

5926

7408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.451

AC:

68491

AN:

151864

Hom.:

16421

Cov.:

AF XY:

0.450

AC XY:

33377

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.601

AC:

24869

AN:

41366

American (AMR)

AF:

0.352

AC:

5374

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1291

AN:

3462

East Asian (EAS)

AF:

0.177

AC:

915

AN:

5174

South Asian (SAS)

AF:

0.231

AC:

1111

AN:

4810

European-Finnish (FIN)

AF:

0.544

AC:

5740

AN:

10542

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.409

AC:

27807

AN:

67946

Other (OTH)

AF:

0.411

AC:

863

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1837

3674

5511

7348

9185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.414

Hom.:

6754

Bravo

AF:

0.445

Asia WGS

AF:

0.250

AC:

871

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.1

(source)

DANN

Benign

0.16

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