rs1988253

Variant names:

• chr22-25566080-T-A
• rs1988253
• NM_005160.4:c.113+927T>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+927T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,168 control chromosomes in the GnomAD database, including 7,745 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 0.22 (7745 hom., cov: 32)
• Consequence: GRK3 NM_005160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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+927T>A		intron	N/A	NP_005151.2	P35626
	GRK3	NM_001362778.2		c.-153+927T>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+927T>A		intron	N/A	ENSP00000317578.4	P35626
	GRK3	ENST00000869559.1		c.113+927T>A		intron	N/A	ENSP00000539618.1
	GRK3	ENST00000947204.1		c.113+927T>A		intron	N/A	ENSP00000617263.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33146 AN: 152050 Hom.: 7698 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.219 AC: 33253 AN: 152168 Hom.: 7745 Cov.: 32 AF XY: 0.214 AC XY: 15917 AN XY: 74412

African (AFR) AF: 0.593 AC: 24563 AN: 41446

American (AMR) AF: 0.107 AC: 1641 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 267 AN: 5192

South Asian (SAS) AF: 0.119 AC: 573 AN: 4826

European-Finnish (FIN) AF: 0.0962 AC: 1019 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4482 AN: 68018

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.158 Hom.: 575

Bravo AF: 0.236

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs1988253; hg19: chr22-25962047;