rs7069375

Positions:

• chr10-119336933-A-G

Variant summary

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

The NM_005308.3(GRK5):​c.148+10322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,022 control chromosomes in the GnomAD database, including 16,642 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 0.43 (16642 hom., cov: 31)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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]

LOC105378511 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.148+10322A>G		intron_variant		ENST00000392870.3
LOC105378511	XR_946357.4	n.2388T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.148+10322A>G		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65123 AN: 151904 Hom.: 16648 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.428 AC: 65113 AN: 152022 Hom.: 16642 Cov.: 31 AF XY: 0.428 AC XY: 31764 AN XY: 74286

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.451

Alfa AF: 0.520 Hom.: 12337

Bravo AF: 0.408

Asia WGS AF: 0.312 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.57

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: rs7069375; hg19: chr10-121096445;