rs1801058

Variant names:

• chr4-3037423-T-A
• NM_182982.3:c.1457T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-3037423-T-A
• chr4-3037423-T-C
• chr4-3037423-T-G

Variant summary

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

The NM_182982.3(GRK4):​c.1457T>A​(p.Val486Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V486A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GRK4 NM_182982.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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

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 (MetaRNN=0.04578355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK4	NM_182982.3	c.1457T>A	p.Val486Glu	missense_variant	Exon 14 of 16	ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.1457T>A	p.Val486Glu	missense_variant	Exon 14 of 16	1	NM_182982.3	ENSP00000381129.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458468 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 725072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.52
DEOGEN2	Benign	0.17	.;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.046	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.085	.;N;.;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.55	P;B;B;P
Vest4		0.24
MutPred		0.42		.;Loss of methylation at K488 (P = 0.0445);.;Loss of methylation at K488 (P = 0.0445);
MVP		0.081
MPC		0.11
ClinPred		0.83	D
GERP RS		-6.2
Varity_R		0.20
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-3039150;