14-96797538-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003384.3(VRK1):​c.-6+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 151,864 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 64 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

VRK1
NM_003384.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 14-96797538-C-T is Benign according to our data. Variant chr14-96797538-C-T is described in ClinVar as [Benign]. Clinvar id is 1272009.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0148 (2240/151864) while in subpopulation AFR AF = 0.051 (2115/41490). AF 95% confidence interval is 0.0492. There are 64 homozygotes in GnomAd4. There are 1080 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VRK1NM_003384.3 linkc.-6+91C>T intron_variant Intron 1 of 12 ENST00000216639.8 NP_003375.1 Q99986

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VRK1ENST00000216639.8 linkc.-6+91C>T intron_variant Intron 1 of 12 1 NM_003384.3 ENSP00000216639.3 Q99986

Frequencies

GnomAD3 genomes
AF:
0.0148
AC:
2239
AN:
151756
Hom.:
64
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0511
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00617
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.0101
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
58
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
48
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2
South Asian (SAS)
AF:
0.00
AC:
0
AN:
8
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
48
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome
AF:
0.0147
AC:
2240
AN:
151864
Hom.:
64
Cov.:
31
AF XY:
0.0145
AC XY:
1080
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.0510
AC:
2115
AN:
41490
American (AMR)
AF:
0.00616
AC:
94
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5148
South Asian (SAS)
AF:
0.000415
AC:
2
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10456
Middle Eastern (MID)
AF:
0.00342
AC:
1
AN:
292
European-Non Finnish (NFE)
AF:
0.000103
AC:
7
AN:
67904
Other (OTH)
AF:
0.00996
AC:
21
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
107
214
322
429
536
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
22
44
66
88
110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0111
Hom.:
6
Bravo
AF:
0.0168
Asia WGS
AF:
0.00494
AC:
17
AN:
3456

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 26, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.9
DANN
Benign
0.95
PhyloP100
-1.2
PromoterAI
-0.20
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs148411927; hg19: chr14-97263875; API