NM_182982.3:c.1683+347T>C

Variant names:

• chr4-3038860-T-C
• rs2798303
• NM_182982.3:c.1683+347T>C

Variant summary

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

The NM_182982.3(GRK4):​c.1683+347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 213,950 control chromosomes in the GnomAD database, including 37,199 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 0.59 (26782 hom., cov: 33)
  • Exomes 𝑓: 0.57 (10417 hom.)
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK4	NM_182982.3	c.1683+347T>C		intron_variant	Intron 15 of 15	ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.1683+347T>C		intron_variant	Intron 15 of 15	1	NM_182982.3	ENSP00000381129.4

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89556 AN: 152060 Hom.: 26753 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.621

GnomAD4 exome AF: 0.573 AC: 35393 AN: 61772 Hom.: 10417 Cov.: 0 AF XY: 0.581 AC XY: 18794 AN XY: 32350

Gnomad4 AFR exome AF: 0.637

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.589 AC: 89639 AN: 152178 Hom.: 26782 Cov.: 33 AF XY: 0.589 AC XY: 43788 AN XY: 74392

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.617

Alfa AF: 0.601 Hom.: 6534

Bravo AF: 0.599

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.51

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: rs2798303; hg19: chr4-3040587;