rs1268947

Variant names:

• chr10-119373119-G-C
• rs1268947
• NM_005308.3:c.149-7696G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005308.3(GRK5):​c.149-7696G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,262 control chromosomes in the GnomAD database, including 2,719 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 0.17 (2719 hom., cov: 33)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK5	NM_005308.3	c.149-7696G>C		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.149-7696G>C		intron_variant	Intron 2 of 15	1	NM_005308.3	ENSP00000376609.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26274 AN: 152144 Hom.: 2712 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.173 AC: 26304 AN: 152262 Hom.: 2719 Cov.: 33 AF XY: 0.176 AC XY: 13089 AN XY: 74456

African (AFR) AF: 0.239 AC: 9911 AN: 41540

American (AMR) AF: 0.165 AC: 2525 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2162 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1436 AN: 4830

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8343 AN: 68022

Other (OTH) AF: 0.150 AC: 318 AN: 2116

Alfa AF: 0.150 Hom.: 234

Bravo AF: 0.179

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.54
PhyloP100		1.8
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: rs1268947; hg19: chr10-121132631;