rs2105380

Positions:

• chr4-2981202-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.53-3311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 152,332 control chromosomes in the GnomAD database, including 188 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 0.042 (188 hom., cov: 33)
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK4	NM_182982.3	c.53-3311C>T		intron_variant		ENST00000398052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK4	ENST00000398052.9	c.53-3311C>T		intron_variant		1	NM_182982.3	P1
GRK4	ENST00000345167.10	c.53-7525C>T		intron_variant		1
GRK4	ENST00000398051.8	c.53-7525C>T		intron_variant		1
GRK4	ENST00000504933.1	c.53-3311C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 152214 Hom.: 189 Cov.: 33

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0415 AC: 6328 AN: 152332 Hom.: 188 Cov.: 33 AF XY: 0.0412 AC XY: 3070 AN XY: 74498

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00724

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0371 Hom.: 19

Bravo AF: 0.0409

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2105380; hg19: chr4-2982929; COSMIC: COSV61671271;