14-96879469-G-A

Position:

• chr14-96879469-G-A

Variant summary

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

The NM_003384.3(VRK1):​c.1160-1708G>A 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 151,874 control chromosomes in the GnomAD database, including 29,555 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 (29555 hom., cov: 31)
• Consequence: VRK1 NM_003384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VRK1	NM_003384.3	c.1160-1708G>A		intron_variant		ENST00000216639.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VRK1	ENST00000216639.8	c.1160-1708G>A		intron_variant		1	NM_003384.3	P4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93448 AN: 151756 Hom.: 29532 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.616 AC: 93511 AN: 151874 Hom.: 29555 Cov.: 31 AF XY: 0.613 AC XY: 45449 AN XY: 74202

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.600

Alfa AF: 0.619 Hom.: 34077

Bravo AF: 0.609

Asia WGS AF: 0.429 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.038
DANN	Benign	0.26

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: rs4905558; hg19: chr14-97345806;