14-96869691-C-T

Position:

• chr14-96869691-C-T

Variant summary

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

The NM_003384.3(VRK1):​c.1069-6339C>T 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 151,846 control chromosomes in the GnomAD database, including 29,611 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 0.62 (29611 hom., cov: 31)
• Consequence: VRK1 NM_003384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK1	NM_003384.3	c.1069-6339C>T		intron_variant		ENST00000216639.8	NP_003375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000216639.8	c.1069-6339C>T		intron_variant		1	NM_003384.3	ENSP00000216639.3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93521 AN: 151728 Hom.: 29588 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.616 AC: 93584 AN: 151846 Hom.: 29611 Cov.: 31 AF XY: 0.613 AC XY: 45500 AN XY: 74220

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.602

Alfa AF: 0.439 Hom.: 890

Bravo AF: 0.610

Asia WGS AF: 0.429 AC: 1492 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.18

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: rs1957137; hg19: chr14-97336028;