14-96810668-C-G

Position:

• chr14-96810668-C-G

Variant summary

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

The NM_003384.3(VRK1):​c.-6+13221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,124 control chromosomes in the GnomAD database, including 3,334 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 0.15 (3334 hom., cov: 31)
• Consequence: VRK1 NM_003384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK1	NM_003384.3	c.-6+13221C>G		intron_variant		ENST00000216639.8	NP_003375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000216639.8	c.-6+13221C>G		intron_variant		1	NM_003384.3	ENSP00000216639	P4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22946 AN: 152006 Hom.: 3318 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.151 AC: 22991 AN: 152124 Hom.: 3334 Cov.: 31 AF XY: 0.160 AC XY: 11860 AN XY: 74350

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.163

Alfa AF: 0.0550 Hom.: 39

Bravo AF: 0.165

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.84

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: rs722869; hg19: chr14-97277005;