NM_182982.3:c.601-1835A>G

Variant names:

• chr4-3011853-A-G
• rs6846128
• NM_182982.3:c.601-1835A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182982.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK4	NM_182982.3	MANE Select	c.601-1835A>G		intron	N/A	NP_892027.2
	GRK4	NM_001004056.2		c.505-1835A>G		intron	N/A	NP_001004056.1
	GRK4	NM_001004057.2		c.601-1835A>G		intron	N/A	NP_001004057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRK4	ENST00000398052.9	TSL:1 MANE Select	c.601-1835A>G		intron	N/A	ENSP00000381129.4
	GRK4	ENST00000345167.10	TSL:1	c.505-1835A>G		intron	N/A	ENSP00000264764.8
	GRK4	ENST00000504933.1	TSL:1	c.601-1835A>G		intron	N/A	ENSP00000427445.1

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

African (AFR) AF: 0.131 AC: 5446 AN: 41538

American (AMR) AF: 0.0321 AC: 491 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00786 AC: 38 AN: 4832

European-Finnish (FIN) AF: 0.0499 AC: 530 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2021 AN: 68028

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.40
PhyloP100		-1.6
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: rs6846128; hg19: chr4-3013580;