14-96927348-C-T

Variant names:

• chr14-96927348-C-T
• rs8016620
• ENST00000680335.1:c.1069-3983C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680335.1(VRK1):​c.1069-3983C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,230 control chromosomes in the GnomAD database, including 64,701 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 0.91 (64701 hom., cov: 32)
• Consequence: VRK1 ENST00000680335.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 3 publications found

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]

VRK1 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 1A

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics, Genomics England PanelApp
• microcephaly-complex motor and sensory axonal neuropathy syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000680335.1	c.1069-3983C>T		intron_variant	Intron 11 of 11			ENSP00000505806.1
VRK1	ENST00000679365.1	n.1151-3983C>T		intron_variant	Intron 11 of 13			ENSP00000505882.1
VRK1	ENST00000679758.1	n.1069-16169C>T		intron_variant	Intron 11 of 12			ENSP00000505539.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138886 AN: 152112 Hom.: 64687 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.991

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.913 AC: 138951 AN: 152230 Hom.: 64701 Cov.: 32 AF XY: 0.918 AC XY: 68295 AN XY: 74428

African (AFR) AF: 0.703 AC: 29117 AN: 41446

American (AMR) AF: 0.967 AC: 14810 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3420 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5188

South Asian (SAS) AF: 0.991 AC: 4777 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10628

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67882 AN: 68048

Other (OTH) AF: 0.920 AC: 1944 AN: 2112

Alfa AF: 0.957 Hom.: 113514

Bravo AF: 0.899

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.079
DANN	Benign	0.82
PhyloP100		-0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8016620; hg19: chr14-97393685;