GRK5 p.Arg304His

Variant names:

• chr10-119436823-G-A
• rs2230349
• NM_005308.3:c.911G>A
• GRK5 p.Arg304His

Your query was ambiguous. Multiple possible variants found:

• chr10-119436823-G-A
• chr10-119436823-GT-AC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.082 (762 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9990 hom.)
• Consequence: GRK5 NM_005308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 34 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.911G>A	p.Arg304His	missense	Exon 9 of 16	NP_005299.1	P34947

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	ENST00000392870.3	TSL:1 MANE Select	c.911G>A	p.Arg304His	missense	Exon 9 of 16	ENSP00000376609.2	P34947
	GRK5	ENST00000857196.1		c.911G>A	p.Arg304His	missense	Exon 9 of 16	ENSP00000527255.1
	GRK5	ENST00000857197.1		c.911G>A	p.Arg304His	missense	Exon 9 of 16	ENSP00000527256.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12438 AN: 152096 Hom.: 762 Cov.: 33

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

GnomAD2 exomes AF: 0.109 AC: 26723 AN: 246198 AF XY: 0.112

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 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.: 32 AF XY: 0.111 AC XY: 80554 AN XY: 723562

African (AFR) AF: 0.0159 AC: 530 AN: 33382

American (AMR) AF: 0.0923 AC: 4094 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 1470 AN: 25664

East Asian (EAS) AF: 0.256 AC: 10132 AN: 39612

South Asian (SAS) AF: 0.163 AC: 13959 AN: 85470

European-Finnish (FIN) AF: 0.0603 AC: 3201 AN: 53128

Middle Eastern (MID) AF: 0.0579 AC: 331 AN: 5718

European-Non Finnish (NFE) AF: 0.108 AC: 119755 AN: 1108404

Other (OTH) AF: 0.108 AC: 6520 AN: 60104

GnomAD4 genome AF: 0.0818 AC: 12445 AN: 152214 Hom.: 762 Cov.: 33 AF XY: 0.0817 AC XY: 6079 AN XY: 74410

African (AFR) AF: 0.0198 AC: 824 AN: 41564

American (AMR) AF: 0.0831 AC: 1271 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1402 AN: 5136

South Asian (SAS) AF: 0.174 AC: 838 AN: 4818

European-Finnish (FIN) AF: 0.0575 AC: 610 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7081 AN: 68006

Other (OTH) AF: 0.0725 AC: 153 AN: 2110

Alfa AF: 0.0971 Hom.: 2777

Bravo AF: 0.0795

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.57	N
PhyloP100		4.1
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.058
Sift	Uncertain	0.021	D
Sift4G	Benign	0.11	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.28
Mutation Taster		=69/31	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230349;

hg19: chr10-121196335;

COSMIC: COSV64867088;