14-96815410-G-A

Position:

• chr14-96815410-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.-6+17963G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,102 control chromosomes in the GnomAD database, including 687 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 0.083 (687 hom., cov: 31)
• Consequence: VRK1 NM_003384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VRK1	NM_003384.3	c.-6+17963G>A		intron_variant		ENST00000216639.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VRK1	ENST00000216639.8	c.-6+17963G>A		intron_variant		1	NM_003384.3	P4

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12638 AN: 151986 Hom.: 686 Cov.: 31

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0831 AC: 12636 AN: 152102 Hom.: 687 Cov.: 31 AF XY: 0.0816 AC XY: 6071 AN XY: 74368

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0739

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.101 Hom.: 99

Bravo AF: 0.0796

Asia WGS AF: 0.0290 AC: 101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.46
DANN	Benign	0.49

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: rs78043256; hg19: chr14-97281747;