rs738344

Variant names:

• chr22-25582389-G-A
• rs738344
• NM_005160.4:c.113+17236G>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+17236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 152,192 control chromosomes in the GnomAD database, including 28 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 0.013 (28 hom., cov: 32)
• Consequence: GRK3 NM_005160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• 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=-0.91).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3	NM_005160.4	MANE Select	c.113+17236G>A		intron	N/A	NP_005151.2
	GRK3	NM_001362778.2		c.-153+17236G>A		intron	N/A	NP_001349707.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK3	ENST00000324198.11	TSL:1 MANE Select	c.113+17236G>A		intron	N/A	ENSP00000317578.4
	GRK3	ENST00000455558.2	TSL:5	n.47+17236G>A		intron	N/A	ENSP00000393688.2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1940 AN: 152080 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0585

Gnomad FIN AF: 0.00916

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0128 AC: 1944 AN: 152192 Hom.: 28 Cov.: 32 AF XY: 0.0128 AC XY: 952 AN XY: 74428

African (AFR) AF: 0.00323 AC: 134 AN: 41530

American (AMR) AF: 0.0111 AC: 169 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.0594 AC: 286 AN: 4816

European-Finnish (FIN) AF: 0.00916 AC: 97 AN: 10594

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0150 AC: 1022 AN: 68008

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.0144 Hom.: 2

Bravo AF: 0.0119

Asia WGS AF: 0.0280 AC: 96 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		0.14
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: rs738344; hg19: chr22-25978356;