rs2275036

chr10-119380809-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005308.3(GRK5):c.149-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,582,214 control chromosomes in the GnomAD database, including 18,406 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1815 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16591 hom.)
• Consequence: GRK5 NM_005308.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001100
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.149-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000392870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.149-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22516 AN: 152126 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.153 AC: 38398 AN: 250208 Hom.: 3734 AF XY: 0.156 AC XY: 21163 AN XY: 135234

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.0710

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.143 AC: 204713 AN: 1429970 Hom.: 16591 Cov.: 26 AF XY: 0.145 AC XY: 103121 AN XY: 710862

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0759

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.148 AC: 22522 AN: 152244 Hom.: 1815 Cov.: 32 AF XY: 0.148 AC XY: 10985 AN XY: 74432

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.161

Alfa AF: 0.134 Hom.: 2353

Bravo AF: 0.146

Asia WGS AF: 0.268 AC: 931 AN: 3478

EpiCase AF: 0.134

EpiControl AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	14
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0080
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: rs2275036; hg19: chr10-121140321; COSMIC: COSV64868009; COSMIC: COSV64868009;