Genetic Variant PVT1:n.1177-20621C>A (chr8-128049539-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000522414.2(PVT1):n.152C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 152,228 control chromosomes in the GnomAD database, including 171 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 0.031 ( 171 hom., cov: 32)

Consequence

PVT1
ENST00000522414.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Publications

7 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]

PVT1 links:

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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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522414.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
PVT1	NR_190187.1	MANE Select	n.1177-20621C>A	intron	N/A
PVT1	NR_003367.4		n.1222-20621C>A	intron	N/A
PVT1	NR_186119.1		n.1841-20621C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
PVT1	ENST00000667305.2	MANE Select	n.1177-20621C>A	intron	N/A
PVT1	ENST00000513868.6	TSL:1	n.972-20621C>A	intron	N/A
PVT1	ENST00000522414.2	TSL:2	n.152C>A	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4748

AN:

152110

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0651

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.0464

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0220

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

GnomAD4 genome

AF:

0.0312

AC:

4751

AN:

152228

Hom.:

171

Cov.:

AF XY:

0.0352

AC XY:

2617

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0199

AC:

826

AN:

41560

American (AMR)

AF:

0.0648

AC:

991

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

955

AN:

5162

South Asian (SAS)

AF:

0.0620

AC:

298

AN:

4810

European-Finnish (FIN)

AF:

0.0464

AC:

492

AN:

10604

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0140

AC:

953

AN:

68006

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0216

Hom.:

185

Bravo

AF:

0.0326

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.3

(source)

DANN

Benign

0.82

PhyloP100

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over