rs12274774

Variant names:

• chr11-67279030-C-A
• rs12274774
• NM_001619.5:c.191-170C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67279030-C-A
• chr11-67279030-C-G
• chr11-67279030-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001619.5(GRK2):​c.191-170C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,264 control chromosomes in the GnomAD database, including 3,082 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 (3082 hom., cov: 33)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Jeune syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK2	NM_001619.5	c.191-170C>A		intron_variant	Intron 2 of 20	ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.101-170C>A		intron_variant	Intron 2 of 20		XP_011543075.1
GRK2	XR_007062455.1	n.418-170C>A		intron_variant	Intron 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK2	ENST00000308595.10	c.191-170C>A		intron_variant	Intron 2 of 20	1	NM_001619.5	ENSP00000312262.5
GRK2	ENST00000526285.1	c.191-170C>A		intron_variant	Intron 2 of 13	5		ENSP00000434126.1
GRK2	ENST00000416281.6	n.813-170C>A		intron_variant	Intron 1 of 16	2
GRK2	ENST00000530291.5	n.149-170C>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18268 AN: 152146 Hom.: 3071 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0894

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

GnomAD4 genome AF: 0.120 AC: 18313 AN: 152264 Hom.: 3082 Cov.: 33 AF XY: 0.116 AC XY: 8655 AN XY: 74450

African (AFR) AF: 0.377 AC: 15638 AN: 41520

American (AMR) AF: 0.0516 AC: 790 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.0542 AC: 281 AN: 5186

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4824

European-Finnish (FIN) AF: 0.0223 AC: 237 AN: 10630

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1063 AN: 68016

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0368 Hom.: 873

Bravo AF: 0.133

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
Mutation Taster		=100/0	polymorphism (auto)

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: rs12274774; hg19: chr11-67046501;