rs2145635

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003384.3(VRK1):c.45A>G(p.Ala15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,613,514 control chromosomes in the GnomAD database, including 116,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8727 hom., cov: 33)

Exomes 𝑓: 0.38 ( 107522 hom. )

Consequence

VRK1
NM_003384.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.762

Variant links:

Genes affected

VRK1 (HGNC:12718): (VRK serine/threonine kinase 1) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and c-JUN. [provided by RefSeq, Jul 2008]

VRK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-96833516-A-G is Benign according to our data. Variant chr14-96833516-A-G is described in ClinVar as [Benign]. Clinvar id is 130731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-96833516-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.762 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK1	NM_003384.3 linkuse as main transcript	c.45A>G	p.Ala15=	synonymous_variant	2/13	ENST00000216639.8	NP_003375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000216639.8 linkuse as main transcript	c.45A>G	p.Ala15=	synonymous_variant	2/13	1	NM_003384.3	ENSP00000216639	P4

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49639

AN:

152006

Hom.:

8729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.326

GnomAD3 exomes

AF:

0.356

AC:

89305

AN:

251022

Hom.:

16884

AF XY:

0.366

AC XY:

49684

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.378

AC:

553130

AN:

1461390

Hom.:

107522

Cov.:

AF XY:

0.381

AC XY:

276643

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.326

AC:

49657

AN:

152124

Hom.:

8727

Cov.:

AF XY:

0.331

AC XY:

24636

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.373

Hom.:

12559

Bravo

AF:

0.315

Asia WGS

AF:

0.256

AC:

889

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.383

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pontocerebellar hypoplasia type 1A

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Isolated microphthalmia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.7

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over