11-67282652-T-G

Position:

• chr11-67282652-T-G

Variant summary

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

The NM_001619.5(GRK2):​c.1161-100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,558,820 control chromosomes in the GnomAD database, including 5,868 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 0.12 (3083 hom., cov: 32)
  • Exomes 𝑓: 0.026 (2785 hom.)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

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]

GRK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK2	NM_001619.5	c.1161-100T>G		intron_variant		ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.1071-100T>G		intron_variant			XP_011543075.1
GRK2	XR_007062455.1	n.1388-100T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10	c.1161-100T>G		intron_variant		1	NM_001619.5	ENSP00000312262.5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18300 AN: 152042 Hom.: 3073 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0547

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0895

GnomAD4 exome AF: 0.0256 AC: 36065 AN: 1406660 Hom.: 2785 Cov.: 25 AF XY: 0.0241 AC XY: 16862 AN XY: 700058

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0366

GnomAD4 genome AF: 0.121 AC: 18348 AN: 152160 Hom.: 3083 Cov.: 32 AF XY: 0.117 AC XY: 8678 AN XY: 74402

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.100 Hom.: 433

Bravo AF: 0.133

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.74

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: rs3730145; hg19: chr11-67050123; COSMIC: COSV57952720; COSMIC: COSV57952720;