Variant rs2230345 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.122A>T(p.Gln41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 1,613,872 control chromosomes in the GnomAD database, including 3,290 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 0.086 ( 1475 hom., cov: 33)

Exomes 𝑓: 0.022 ( 1815 hom. )

Consequence

GRK5
NM_005308.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

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=0.0019470751).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK5	NM_005308.3 linkuse as main transcript	c.122A>T	p.Gln41Leu	missense_variant	2/16	ENST00000392870.3	NP_005299.1	P34947

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3 linkuse as main transcript	c.122A>T	p.Gln41Leu	missense_variant	2/16	1	NM_005308.3	ENSP00000376609.2		P34947

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13132

AN:

152150

Hom.:

1473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0681

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0765

GnomAD3 exomes

AF:

0.0375

AC:

9435

AN:

251406

Hom.:

709

AF XY:

0.0341

AC XY:

4628

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.0110

Gnomad SAS exome

AF:

0.0626

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0140

Gnomad OTH exome

AF:

0.0311

GnomAD4 exome

AF:

0.0225

AC:

32876

AN:

1461604

Hom.:

1815

Cov.:

AF XY:

0.0227

AC XY:

16484

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.00688

Gnomad4 SAS exome

AF:

0.0606

Gnomad4 FIN exome

AF:

0.00962

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.0375

GnomAD4 genome

AF:

0.0864

AC:

13159

AN:

152268

Hom.:

1475

Cov.:

AF XY:

0.0828

AC XY:

6169

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.0446

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0677

Gnomad4 FIN

AF:

0.00847

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0757

Alfa

AF:

0.0245

Hom.:

184

Bravo

AF:

0.0974

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.265

AC:

1166

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.0430

AC:

5221

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

EpiCase

AF:

0.0143

EpiControl

AF:

0.0154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.10

Sift

Benign

0.10

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.12

MPC

0.21

ClinPred

0.037

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.63

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