rs7093673

chr10-119222844-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005308.3(GRK5):c.52+14875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,032 control chromosomes in the GnomAD database, including 7,483 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 0.31 (7483 hom., cov: 32)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.52+14875C>T		intron_variant		ENST00000392870.3
GRK5	XM_005269707.3	c.52+14875C>T		intron_variant
GRK5	XM_005269708.2	c.52+14875C>T		intron_variant
GRK5	XM_047425120.1	c.-264+14194C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.52+14875C>T		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47414 AN: 151914 Hom.: 7470 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.312 AC: 47476 AN: 152032 Hom.: 7483 Cov.: 32 AF XY: 0.310 AC XY: 23073 AN XY: 74322

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.308

Alfa AF: 0.309 Hom.: 9684

Bravo AF: 0.318

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.6
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs7093673; hg19: chr10-120982356;