ENST00000513868.6:n.541-3663T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000513868.6(PVT1):​n.541-3663T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,928 control chromosomes in the GnomAD database, including 18,346 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 0.47 ( 18346 hom., cov: 31)

Consequence

PVT1
ENST00000513868.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

5 publications found
Variant links:
Genes affected
PVT1 (HGNC:9709): (Pvt1 oncogene) This gene represents a long non-coding RNA locus that has been identified as a candidate oncogene. Increased copy number and overexpression of this gene are associated with many types of cancers including breast and ovarian cancers, acute myeloid leukemia and Hodgkin lymphoma. Allelic variants of this gene are also associated with end-stage renal disease attributed to type 1 diabetes. Consistent with its association with various types of cancer, transcription of this gene is regulated by the tumor suppressor p53 through a canonical p53-binding site, and it has been implicated in regulating levels of the proto-oncogene MYC to promote tumorigenesis. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PVT1NR_003367.4 linkn.791-3663T>C intron_variant Intron 3 of 8
PVT1NR_186119.1 linkn.956-3663T>C intron_variant Intron 4 of 14
PVT1NR_186120.1 linkn.906-2119T>C intron_variant Intron 4 of 14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PVT1ENST00000513868.6 linkn.541-3663T>C intron_variant Intron 2 of 7 1
PVT1ENST00000517525.2 linkn.955-8921T>C intron_variant Intron 4 of 5 3
PVT1ENST00000517790.2 linkn.1274-8921T>C intron_variant Intron 2 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.474
AC:
71968
AN:
151810
Hom.:
18338
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.293
Gnomad AMI
AF:
0.604
Gnomad AMR
AF:
0.617
Gnomad ASJ
AF:
0.550
Gnomad EAS
AF:
0.639
Gnomad SAS
AF:
0.701
Gnomad FIN
AF:
0.573
Gnomad MID
AF:
0.652
Gnomad NFE
AF:
0.501
Gnomad OTH
AF:
0.516
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.474
AC:
71995
AN:
151928
Hom.:
18346
Cov.:
31
AF XY:
0.487
AC XY:
36158
AN XY:
74260
show subpopulations
African (AFR)
AF:
0.292
AC:
12107
AN:
41430
American (AMR)
AF:
0.618
AC:
9440
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.550
AC:
1908
AN:
3470
East Asian (EAS)
AF:
0.638
AC:
3299
AN:
5172
South Asian (SAS)
AF:
0.700
AC:
3363
AN:
4802
European-Finnish (FIN)
AF:
0.573
AC:
6038
AN:
10530
Middle Eastern (MID)
AF:
0.650
AC:
191
AN:
294
European-Non Finnish (NFE)
AF:
0.501
AC:
34012
AN:
67946
Other (OTH)
AF:
0.517
AC:
1089
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1852
3704
5557
7409
9261
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
664
1328
1992
2656
3320
<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:
0.501
Hom.:
31133
Bravo
AF:
0.466
Asia WGS
AF:
0.609
AC:
2118
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.7
DANN
Benign
0.67
PhyloP100
1.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs11993333; hg19: chr8-128992487; API