22-25727521-C-T

Position:

• chr22-25727521-C-T

Variant summary

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

The NM_005160.4(GRK3):​c.*5071C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 152,358 control chromosomes in the GnomAD database, including 72,993 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 0.98 (72993 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: GRK3 NM_005160.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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 (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK3	NM_005160.4	c.*5071C>T		3_prime_UTR_variant	21/21	ENST00000324198.11
GRK3	NM_001362778.2	c.*5071C>T		3_prime_UTR_variant	20/20
GRK3	XM_011529975.3	c.*5071C>T		3_prime_UTR_variant	18/18
GRK3	XM_047441166.1	c.*5071C>T		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK3	ENST00000324198.11	c.*5071C>T		3_prime_UTR_variant	21/21	1	NM_005160.4	P1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149000 AN: 152240 Hom.: 72932 Cov.: 34

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.963

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.979 AC: 149120 AN: 152358 Hom.: 72993 Cov.: 34 AF XY: 0.980 AC XY: 73020 AN XY: 74506

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.993

Gnomad4 FIN AF: 0.992

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.963

Alfa AF: 0.967 Hom.: 63872

Bravo AF: 0.977

Asia WGS AF: 0.994 AC: 3454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.48

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: rs133839; hg19: chr22-26123488;