chr10-119255615-G-A

Variant names:

• chr10-119255615-G-A
• rs4752266
• NM_005308.3:c.52+47646G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 (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 rank	MANE	Protein	UniProt
GRK5	NM_005308.3	c.52+47646G>A		intron_variant	Intron 1 of 15	ENST00000392870.3	NP_005299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.52+47646G>A		intron_variant	Intron 1 of 15	1	NM_005308.3	ENSP00000376609.2

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

African (AFR) AF: 0.471 AC: 19547 AN: 41474

American (AMR) AF: 0.651 AC: 9936 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2631 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4306 AN: 5172

South Asian (SAS) AF: 0.791 AC: 3811 AN: 4820

European-Finnish (FIN) AF: 0.791 AC: 8363 AN: 10578

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50799 AN: 67950

Other (OTH) AF: 0.685 AC: 1446 AN: 2112

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
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs4752266; hg19: chr10-121015127;