rs4752266

chr10-119255615-G-Achr10-119255615-G-C

Variant summary

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

The NM_005308.3(GRK5):c.52+47646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,044 control chromosomes in the GnomAD database, including 35,452 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 0.67 (35452 hom., cov: 31)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.52+47646G>A		intron_variant		ENST00000392870.3
GRK5	XM_005269707.3	c.52+47646G>A		intron_variant
GRK5	XM_005269708.2	c.52+47646G>A		intron_variant
GRK5	XM_047425120.1	c.-264+46965G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.52+47646G>A		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101828 AN: 151926 Hom.: 35448 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.670 AC: 101871 AN: 152044 Hom.: 35452 Cov.: 31 AF XY: 0.673 AC XY: 50004 AN XY: 74296

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.685

Alfa AF: 0.710 Hom.: 4919

Bravo AF: 0.645

Asia WGS AF: 0.757 AC: 2632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.84
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4752266; hg19: chr10-121015127;