rs78043256

Variant names:

• chr14-96815410-G-A
• rs78043256
• NM_003384.3:c.-6+17963G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.93).
• 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 rank	MANE	Protein	UniProt
VRK1	NM_003384.3	c.-6+17963G>A		intron_variant	Intron 1 of 12	ENST00000216639.8	NP_003375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000216639.8	c.-6+17963G>A		intron_variant	Intron 1 of 12	1	NM_003384.3	ENSP00000216639.3

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

African (AFR) AF: 0.0222 AC: 922 AN: 41480

American (AMR) AF: 0.0739 AC: 1129 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 306 AN: 3472

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5186

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4824

European-Finnish (FIN) AF: 0.0933 AC: 986 AN: 10572

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8613 AN: 67966

Other (OTH) AF: 0.0852 AC: 180 AN: 2112

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
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78043256; hg19: chr14-97281747;