rs3730310

Positions:

• chr11-67279929-G-C

Variant summary

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

The NM_001619.5(GRK2):​c.503+29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,605,810 control chromosomes in the GnomAD database, including 3,605 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 0.087 (1941 hom., cov: 33)
  • Exomes 𝑓: 0.0085 (1664 hom.)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK2	NM_001619.5	c.503+29G>C		intron_variant		ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.413+29G>C		intron_variant			XP_011543075.1
GRK2	XR_007062455.1	n.730+29G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10	c.503+29G>C		intron_variant		1	NM_001619.5	ENSP00000312262	P1
GRK2	ENST00000526285.1	c.503+29G>C		intron_variant		5		ENSP00000434126
GRK2	ENST00000416281.6	n.1125+29G>C		intron_variant, non_coding_transcript_variant		2
GRK2	ENST00000529738.1	n.183+29G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13212 AN: 152146 Hom.: 1939 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0583

GnomAD3 exomes AF: 0.0219 AC: 5458 AN: 249132 Hom.: 737 AF XY: 0.0159 AC XY: 2148 AN XY: 135206

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000491

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000712

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00854 AC: 12415 AN: 1453546 Hom.: 1664 Cov.: 29 AF XY: 0.00728 AC XY: 5267 AN XY: 723584

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000511

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000379

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0869 AC: 13232 AN: 152264 Hom.: 1941 Cov.: 33 AF XY: 0.0830 AC XY: 6182 AN XY: 74460

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0446 Hom.: 160

Bravo AF: 0.0972

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.042
DANN	Benign	0.24
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		2.1

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: rs3730310; hg19: chr11-67047400;