4-2986909-C-T

Position:

• chr4-2986909-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182982.3(GRK4):​c.149-1818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 300,206 control chromosomes in the GnomAD database, including 26,715 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 0.45 (16421 hom., cov: 31)
  • Exomes 𝑓: 0.36 (10294 hom.)
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

GRK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK4	NM_182982.3	c.149-1818C>T		intron_variant		ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.149-1818C>T		intron_variant		1	NM_182982.3	ENSP00000381129.4
GRK4	ENST00000345167.10	c.53-1818C>T		intron_variant		1		ENSP00000264764.8
GRK4	ENST00000504933.1	c.149-1818C>T		intron_variant		1		ENSP00000427445.1
GRK4	ENST00000398051.8	c.53-1818C>T		intron_variant		1		ENSP00000381128.4

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68420 AN: 151746 Hom.: 16394 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.356 AC: 52820 AN: 148342 Hom.: 10294 AF XY: 0.339 AC XY: 28297 AN XY: 83552

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.451 AC: 68491 AN: 151864 Hom.: 16421 Cov.: 31 AF XY: 0.450 AC XY: 33377 AN XY: 74232

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.411

Alfa AF: 0.411 Hom.: 5917

Bravo AF: 0.445

Asia WGS AF: 0.250 AC: 871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.16

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: rs2488815; hg19: chr4-2988636;