rs713921

Positions:

• chr22-25583267-G-A

Variant summary

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

The NM_005160.4(GRK3):​c.113+18114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 152,208 control chromosomes in the GnomAD database, including 62 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 0.023 (62 hom., cov: 32)
• Consequence: GRK3 NM_005160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK3	NM_005160.4	c.113+18114G>A		intron_variant		ENST00000324198.11	NP_005151.2
GRK3	NM_001362778.2	c.-153+18114G>A		intron_variant			NP_001349707.1
GRK3	XM_047441167.1	c.113+18114G>A		intron_variant			XP_047297123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK3	ENST00000324198.11	c.113+18114G>A		intron_variant		1	NM_005160.4	ENSP00000317578	P1
GRK3	ENST00000455558.2	c.47+18114G>A		intron_variant, NMD_transcript_variant		5		ENSP00000393688

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3435 AN: 152094 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.00927

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0226 AC: 3441 AN: 152208 Hom.: 62 Cov.: 32 AF XY: 0.0222 AC XY: 1651 AN XY: 74408

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0279

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.00927

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0204 Hom.: 3

Bravo AF: 0.0234

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.78

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: rs713921; hg19: chr22-25979234;