rs2857839

Variant names:

• chr4-3034903-T-C
• rs2857839
• NM_182982.3:c.1270-483T>C

Variant summary

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

The NM_182982.3(GRK4):​c.1270-483T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,978 control chromosomes in the GnomAD database, including 32,643 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 0.65 (32643 hom., cov: 31)
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 6 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]

ENSG00000296061 (HGNC:58716):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK4	NM_182982.3	c.1270-483T>C		intron_variant	Intron 12 of 15	ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.1270-483T>C		intron_variant	Intron 12 of 15	1	NM_182982.3	ENSP00000381129.4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98408 AN: 151860 Hom.: 32593 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.648 AC: 98517 AN: 151978 Hom.: 32643 Cov.: 31 AF XY: 0.646 AC XY: 47964 AN XY: 74254

African (AFR) AF: 0.783 AC: 32449 AN: 41460

American (AMR) AF: 0.661 AC: 10087 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2644 AN: 5170

South Asian (SAS) AF: 0.738 AC: 3551 AN: 4810

European-Finnish (FIN) AF: 0.496 AC: 5217 AN: 10526

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40221 AN: 67974

Other (OTH) AF: 0.660 AC: 1394 AN: 2112

Alfa AF: 0.643 Hom.: 4771

Bravo AF: 0.660

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.32
PhyloP100		-0.41
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: rs2857839; hg19: chr4-3036630;