10-119380809-C-T

Variant names:

• chr10-119380809-C-T
• rs2275036
• NM_005308.3:c.149-6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005308.3(GRK5):​c.149-6C>T variant causes a splice region, 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. 3/3 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, intron
• Scores: Splicing: ADA: 0.0001100
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 12 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 -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 rank	MANE	Protein	UniProt
GRK5	NM_005308.3	c.149-6C>T		splice_region_variant, intron_variant	Intron 2 of 15	ENST00000392870.3	NP_005299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.149-6C>T		splice_region_variant, intron_variant	Intron 2 of 15	1	NM_005308.3	ENSP00000376609.2

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

GnomAD2 exomes AF: 0.153 AC: 38398 AN: 250208 AF XY: 0.156

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 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

African (AFR) AF: 0.167 AC: 5512 AN: 32916

American (AMR) AF: 0.0759 AC: 3377 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3121 AN: 25904

East Asian (EAS) AF: 0.382 AC: 15002 AN: 39264

South Asian (SAS) AF: 0.206 AC: 17556 AN: 85338

European-Finnish (FIN) AF: 0.122 AC: 6472 AN: 53246

Middle Eastern (MID) AF: 0.183 AC: 1021 AN: 5586

European-Non Finnish (NFE) AF: 0.133 AC: 143864 AN: 1084068

Other (OTH) AF: 0.149 AC: 8788 AN: 59166

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

African (AFR) AF: 0.168 AC: 6974 AN: 41540

American (AMR) AF: 0.0938 AC: 1435 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1914 AN: 5172

South Asian (SAS) AF: 0.209 AC: 1009 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9029 AN: 68010

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.134 Hom.: 2839

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
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2275036; hg19: chr10-121140321; COSMIC: COSV64868009; COSMIC: COSV64868009;