rs10896164

Positions:

• chr11-67284995-G-A
• chr11-67284995-G-T

Variant summary

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

The NM_001619.5(GRK2):​c.1791+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,612,232 control chromosomes in the GnomAD database, including 667,488 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 0.75 (47745 hom., cov: 32)
  • Exomes 𝑓: 0.91 (619743 hom.)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

GRK2 (HGNC:289): (G protein-coupled receptor kinase 2) This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer's disease. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK2	NM_001619.5	c.1791+12G>A		intron_variant		ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.1701+12G>A		intron_variant			XP_011543075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10	c.1791+12G>A		intron_variant		1	NM_001619.5	ENSP00000312262	P1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114394 AN: 151970 Hom.: 47740 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.800

GnomAD3 exomes AF: 0.836 AC: 206682 AN: 247118 Hom.: 90691 AF XY: 0.862 AC XY: 115977 AN XY: 134490

Gnomad AFR exome AF: 0.367

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.937

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.939

Gnomad FIN exome AF: 0.896

Gnomad NFE exome AF: 0.942

Gnomad OTH exome AF: 0.868

GnomAD4 exome AF: 0.914 AC: 1334684 AN: 1460144 Hom.: 619743 Cov.: 72 AF XY: 0.919 AC XY: 667219 AN XY: 726398

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.939

Gnomad4 FIN exome AF: 0.897

Gnomad4 NFE exome AF: 0.948

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.752 AC: 114426 AN: 152088 Hom.: 47745 Cov.: 32 AF XY: 0.754 AC XY: 56087 AN XY: 74360

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.801

Alfa AF: 0.847 Hom.: 6935

Bravo AF: 0.715

Asia WGS AF: 0.795 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10896164; hg19: chr11-67052466; COSMIC: COSV57754572; COSMIC: COSV57754572;