4-2988771-CGT-TTG

Variant names:

• chr4-2988771-CGT-TTG
• NM_182982.3:c.193_195delCGTinsTTG
• GRK4 p.Arg65Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182982.3(GRK4):​c.193_195delCGTinsTTG​(p.Arg65Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R65C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRK4 NM_182982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.25
• Publications: 0 publications found

Genes affected

GRK4 (HGNC:4543): (G protein-coupled receptor kinase 4) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182982.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK4	NM_182982.3	MANE Select	c.193_195delCGTinsTTG	p.Arg65Leu	missense	N/A	NP_892027.2	P32298-1
	GRK4	NM_001004056.2		c.97_99delCGTinsTTG	p.Arg33Leu	missense	N/A	NP_001004056.1	P32298-2
	GRK4	NM_001004057.2		c.193_195delCGTinsTTG	p.Arg65Leu	missense	N/A	NP_001004057.1	P32298-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK4	ENST00000398052.9	TSL:1 MANE Select	c.193_195delCGTinsTTG	p.Arg65Leu	missense	N/A	ENSP00000381129.4	P32298-1
	GRK4	ENST00000345167.10	TSL:1	c.97_99delCGTinsTTG	p.Arg33Leu	missense	N/A	ENSP00000264764.8	P32298-2
	GRK4	ENST00000504933.1	TSL:1	c.193_195delCGTinsTTG	p.Arg65Leu	missense	N/A	ENSP00000427445.1	P32298-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-2990498;