rs10128498

Variant names:

• chr10-119293396-G-A
• rs10128498
• NM_005308.3:c.53-33120G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-119293396-G-A
• chr10-119293396-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 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.53-33120G>A		intron	N/A	NP_005299.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	ENST00000392870.3	TSL:1 MANE Select	c.53-33120G>A		intron	N/A	ENSP00000376609.2
	GRK5	ENST00000857196.1		c.53-33120G>A		intron	N/A	ENSP00000527255.1
	GRK5	ENST00000857197.1		c.53-33120G>A		intron	N/A	ENSP00000527256.1

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

African (AFR) AF: 0.474 AC: 19651 AN: 41426

American (AMR) AF: 0.533 AC: 8133 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4100 AN: 5180

South Asian (SAS) AF: 0.644 AC: 3104 AN: 4820

European-Finnish (FIN) AF: 0.741 AC: 7845 AN: 10586

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44084 AN: 67958

Other (OTH) AF: 0.580 AC: 1224 AN: 2112

Alfa AF: 0.623 Hom.: 56646

Bravo AF: 0.574

Asia WGS AF: 0.688 AC: 2395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		-0.19
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: rs10128498; hg19: chr10-121052908;