chr10-119431674-C-A

Position:

• chr10-119431674-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.738+147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 942,410 control chromosomes in the GnomAD database, including 135,137 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 0.57 (25872 hom., cov: 33)
  • Exomes 𝑓: 0.52 (109265 hom.)
• Consequence: GRK5 NM_005308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK5	NM_005308.3	c.738+147C>A		intron_variant		ENST00000392870.3	NP_005299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK5	ENST00000392870.3	c.738+147C>A		intron_variant		1	NM_005308.3	ENSP00000376609	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87365 AN: 152044 Hom.: 25831 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.517 AC: 408853 AN: 790248 Hom.: 109265 AF XY: 0.516 AC XY: 205200 AN XY: 397818

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.575 AC: 87461 AN: 152162 Hom.: 25872 Cov.: 33 AF XY: 0.575 AC XY: 42761 AN XY: 74386

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.543

Alfa AF: 0.515 Hom.: 33472

Bravo AF: 0.586

Asia WGS AF: 0.455 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.73

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: rs7099478; hg19: chr10-121191186; COSMIC: COSV64865494;