14-96797592-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003384.3(VRK1):c.-6+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,538 control chromosomes in the GnomAD database, including 29,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29472 hom., cov: 32)
  • Exomes 𝑓: 0.63 (7 hom.)
• Consequence: VRK1 NM_003384.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-96797592-T-C is Benign according to our data. Variant chr14-96797592-T-C is described in ClinVar as [Benign]. Clinvar id is 1251145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VRK1	NM_003384.3	c.-6+145T>C		intron_variant		ENST00000216639.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VRK1	ENST00000216639.8	c.-6+145T>C		intron_variant		1	NM_003384.3	P4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93205 AN: 151394 Hom.: 29456 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.632 AC: 24 AN: 38 Hom.: 7 AF XY: 0.647 AC XY: 22 AN XY: 34

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.616 AC: 93252 AN: 151500 Hom.: 29472 Cov.: 32 AF XY: 0.612 AC XY: 45326 AN XY: 74006

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.600

Alfa AF: 0.631 Hom.: 3790

Bravo AF: 0.608

Asia WGS AF: 0.424 AC: 1468 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.22

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: rs71419296; hg19: chr14-97263929;