rs12415832

chr10-119352815-C-A

Variant summary

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

The NM_005308.3(GRK5):c.148+26204C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 152,252 control chromosomes in the GnomAD database, including 199 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 0.037 (199 hom., cov: 32)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK5	NM_005308.3	c.148+26204C>A		intron_variant		ENST00000392870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK5	ENST00000392870.3	c.148+26204C>A		intron_variant		1	NM_005308.3	P1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5584 AN: 152134 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0368 AC: 5599 AN: 152252 Hom.: 199 Cov.: 32 AF XY: 0.0385 AC XY: 2863 AN XY: 74440

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0925

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.0273

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0321 Hom.: 20

Bravo AF: 0.0416

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.47

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: rs12415832; hg19: chr10-121112327;