10-119278440-C-T

Variant names:

• chr10-119278440-C-T
• rs4752269
• NM_005308.3:c.53-48076C>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.53-48076C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,954 control chromosomes in the GnomAD database, including 4,972 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 0.24 (4972 hom., cov: 30)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.294 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.53-48076C>T		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.53-48076C>T		intron	N/A	ENSP00000376609.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36847 AN: 151836 Hom.: 4968 Cov.: 30

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.243 AC: 36853 AN: 151954 Hom.: 4972 Cov.: 30 AF XY: 0.243 AC XY: 18028 AN XY: 74278

African (AFR) AF: 0.119 AC: 4924 AN: 41476

American (AMR) AF: 0.301 AC: 4596 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1100 AN: 5160

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4806

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10570

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19953 AN: 67900

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.281 Hom.: 26833

Bravo AF: 0.243

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.78
PhyloP100		0.13
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: rs4752269; hg19: chr10-121037952;