Variant rs2230349 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005308.3(GRK5):c.911G>A(p.Arg304His) variant causes a missense change. The variant allele was found at a frequency of 0.107 in 1,608,038 control chromosomes in the GnomAD database, including 10,752 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.082 ( 762 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9990 hom. )

Consequence

GRK5
NM_005308.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016897321).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	9/16	ENST00000392870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	9/16	1	NM_005308.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12438

AN:

152096

Hom.:

762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0830

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.0575

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.109

AC:

26723

AN:

246198

Hom.:

1840

AF XY:

0.112

AC XY:

14925

AN XY:

132916

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.0574

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0587

Gnomad NFE exome

AF:

0.0987

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.110

AC:

159992

AN:

1455824

Hom.:

9990

Cov.:

AF XY:

0.111

AC XY:

80554

AN XY:

723562

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.0923

Gnomad4 ASJ exome

AF:

0.0573

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0603

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.0818

AC:

12445

AN:

152214

Hom.:

762

Cov.:

AF XY:

0.0817

AC XY:

6079

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.0831

Gnomad4 ASJ

AF:

0.0556

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.0575

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0725

Alfa

AF:

0.0994

Hom.:

1000

Bravo

AF:

0.0795

TwinsUK

AF:

0.110

AC:

408

ALSPAC

AF:

0.102

AC:

395

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.0998

AC:

858

ExAC

AF:

0.107

AC:

13035

Asia WGS

AF:

0.155

AC:

539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

MutationTaster

Benign

0.000043

P;P

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.058

Sift

Uncertain

0.021

Sift4G

Benign

0.11

Polyphen

0.068

Vest4

0.098

MPC

1.0

ClinPred

0.043

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over