chr10-119436823-G-A

Variant summary

Our verdict is Benign. The variant received -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.

Frequency

Genomes: 𝑓 0.082 ( 762 hom., cov: 33)
Exomes 𝑓: 0.11 ( 9990 hom. )

Consequence

GRK5
NM_005308.3 missense

Scores

1
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11

Publications

34 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRK5NM_005308.3 linkc.911G>A p.Arg304His missense_variant Exon 9 of 16 ENST00000392870.3 NP_005299.1 P34947

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRK5ENST00000392870.3 linkc.911G>A p.Arg304His missense_variant Exon 9 of 16 1 NM_005308.3 ENSP00000376609.2 P34947

Frequencies

GnomAD3 genomes
AF:
0.0818
AC:
12438
AN:
152096
Hom.:
762
Cov.:
33
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
GnomAD2 exomes
AF:
0.109
AC:
26723
AN:
246198
AF XY:
0.112
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 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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
7456
14912
22369
29825
37281
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4498
8996
13494
17992
22490
<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:
0.0818
AC:
12445
AN:
152214
Hom.:
762
Cov.:
33
AF XY:
0.0817
AC XY:
6079
AN XY:
74410
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
582
1164
1745
2327
2909
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
156
312
468
624
780
<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:
0.0971
Hom.:
2777
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
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
Polyphen
0.068
B
Vest4
0.098
MPC
1.0
ClinPred
0.043
T
GERP RS
3.5
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

Publications

Other links and lift over

dbSNP: rs2230349; hg19: chr10-121196335; COSMIC: COSV64867088; API