rs713921

Variant names:

• chr22-25583267-G-A
• rs713921
• NM_005160.4:c.113+18114G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3	NM_005160.4	MANE Select	c.113+18114G>A		intron	N/A	NP_005151.2	P35626
	GRK3	NM_001362778.2		c.-153+18114G>A		intron	N/A	NP_001349707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3	ENST00000324198.11	TSL:1 MANE Select	c.113+18114G>A		intron	N/A	ENSP00000317578.4	P35626
	GRK3	ENST00000869559.1		c.113+18114G>A		intron	N/A	ENSP00000539618.1
	GRK3	ENST00000947204.1		c.113+18114G>A		intron	N/A	ENSP00000617263.1

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

African (AFR) AF: 0.0373 AC: 1548 AN: 41524

American (AMR) AF: 0.0137 AC: 209 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 97 AN: 3472

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5192

South Asian (SAS) AF: 0.0593 AC: 286 AN: 4820

European-Finnish (FIN) AF: 0.00927 AC: 98 AN: 10576

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1038 AN: 68014

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.0209 Hom.: 3

Bravo AF: 0.0234

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.78
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs713921; hg19: chr22-25979234;