rs10886430

Variant names:

• chr10-119250744-A-G
• rs10886430
• NM_005308.3:c.52+42775A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005308.3(GRK5):​c.52+42775A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,244 control chromosomes in the GnomAD database, including 794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (794 hom., cov: 31)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.273
• Publications: 28 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-119250744-A-G is Benign according to our data. Variant chr10-119250744-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	NM_005308.3	MANE Select	c.52+42775A>G		intron	N/A	NP_005299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK5	ENST00000392870.3	TSL:1 MANE Select	c.52+42775A>G		intron	N/A	ENSP00000376609.2
	GRK5	ENST00000857196.1		c.52+42775A>G		intron	N/A	ENSP00000527255.1
	GRK5	ENST00000857197.1		c.52+42775A>G		intron	N/A	ENSP00000527256.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13304 AN: 152126 Hom.: 793 Cov.: 31

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0874 AC: 13300 AN: 152244 Hom.: 794 Cov.: 31 AF XY: 0.0841 AC XY: 6258 AN XY: 74426

African (AFR) AF: 0.0241 AC: 1000 AN: 41566

American (AMR) AF: 0.0907 AC: 1386 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0484 AC: 234 AN: 4830

European-Finnish (FIN) AF: 0.0885 AC: 937 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8686 AN: 68000

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.101 Hom.: 580

Bravo AF: 0.0850

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.67
PhyloP100		-0.27
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: rs10886430; hg19: chr10-121010256; COSMIC: COSV67313067;