rs10128498

chr10-119293396-G-Achr10-119293396-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005308.3(GRK5):c.53-33120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,024 control chromosomes in the GnomAD database, including 27,864 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 0.60 (27864 hom., cov: 31)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.53-33120G>A		intron_variant		ENST00000392870.3
GRK5	XM_005269707.3	c.53-33120G>A		intron_variant
GRK5	XM_005269708.2	c.52+85427G>A		intron_variant
GRK5	XM_047425120.1	c.-263-33120G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.53-33120G>A		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90810 AN: 151906 Hom.: 27849 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.598 AC: 90861 AN: 152024 Hom.: 27864 Cov.: 31 AF XY: 0.601 AC XY: 44642 AN XY: 74332

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.580

Alfa AF: 0.629 Hom.: 41783

Bravo AF: 0.574

Asia WGS AF: 0.688 AC: 2395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs10128498; hg19: chr10-121052908;