4-3011853-A-G

Position:

• chr4-3011853-A-G

Variant summary

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

The NM_182982.3(GRK4):​c.601-1835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,284 control chromosomes in the GnomAD database, including 425 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 0.057 (425 hom., cov: 32)
• Consequence: GRK4 NM_182982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK4	NM_182982.3	c.601-1835A>G		intron_variant		ENST00000398052.9	NP_892027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRK4	ENST00000398052.9	c.601-1835A>G		intron_variant		1	NM_182982.3	ENSP00000381129.4
GRK4	ENST00000345167.10	c.505-1835A>G		intron_variant		1		ENSP00000264764.8
GRK4	ENST00000504933.1	c.601-1835A>G		intron_variant		1		ENSP00000427445.1
GRK4	ENST00000398051.8	c.505-1835A>G		intron_variant		1		ENSP00000381128.4

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8726 AN: 152166 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0575 AC: 8755 AN: 152284 Hom.: 425 Cov.: 32 AF XY: 0.0568 AC XY: 4226 AN XY: 74466

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00786

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0282 Hom.: 36

Bravo AF: 0.0596

Asia WGS AF: 0.0280 AC: 98 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	0.014
DANN	Benign	0.40

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: rs6846128; hg19: chr4-3013580;