11-67279030-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001619.5(GRK2):​c.191-170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
• Consequence: GRK2 NM_001619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK2	NM_001619.5	c.191-170C>T		intron_variant	Intron 2 of 20	ENST00000308595.10	NP_001610.2
GRK2	XM_011544773.2	c.101-170C>T		intron_variant	Intron 2 of 20		XP_011543075.1
GRK2	XR_007062455.1	n.418-170C>T		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>T		intron_variant	Intron 2 of 20	1	NM_001619.5	ENSP00000312262.5
GRK2	ENST00000526285.1	c.191-170C>T		intron_variant	Intron 2 of 13	5		ENSP00000434126.1
GRK2	ENST00000416281.6	n.813-170C>T		intron_variant	Intron 1 of 16	2
GRK2	ENST00000530291.5	n.149-170C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs12274774; hg19: chr11-67046501;