rs13255292

Positions:

• chr8-128064327-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_003367.3(PVT1):​n.1213-5833C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,202 control chromosomes in the GnomAD database, including 5,452 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 0.24 (5452 hom., cov: 33)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVT1	NR_003367.3	n.1213-5833C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVT1	ENST00000651587.1	n.913-5833C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37173 AN: 152084 Hom.: 5444 Cov.: 33

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.244 AC: 37175 AN: 152202 Hom.: 5452 Cov.: 33 AF XY: 0.245 AC XY: 18246 AN XY: 74412

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.279

Alfa AF: 0.316 Hom.: 10955

Bravo AF: 0.231

Asia WGS AF: 0.206 AC: 716 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13255292; hg19: chr8-129076573;