22-25679039-A-G

Position:

• chr22-25679039-A-G

Variant summary

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

The NM_005160.4(GRK3):​c.747+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 589,346 control chromosomes in the GnomAD database, including 3,774 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 0.11 (2911 hom., cov: 33)
  • Exomes 𝑓: 0.014 (863 hom.)
• Consequence: GRK3 NM_005160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

Genes affected

GRK3 (HGNC:290): (G protein-coupled receptor kinase 3) The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK3	NM_005160.4	c.747+124A>G		intron_variant		ENST00000324198.11	NP_005151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11	c.747+124A>G		intron_variant		1	NM_005160.4	ENSP00000317578.4
GRK3	ENST00000455558.2	n.*469+124A>G		intron_variant		5		ENSP00000393688.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16604 AN: 152058 Hom.: 2903 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.0809

GnomAD4 exome AF: 0.0139 AC: 6078 AN: 437172 Hom.: 863 AF XY: 0.0119 AC XY: 2748 AN XY: 230640

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.000149

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00138

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.109 AC: 16649 AN: 152174 Hom.: 2911 Cov.: 33 AF XY: 0.106 AC XY: 7872 AN XY: 74406

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00204

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.0843 Hom.: 235

Bravo AF: 0.125

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.51

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: rs3730109; hg19: chr22-26075006;