rs13249999

Positions:

• chr8-128037201-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.1213-32959C>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 0.0596 in 152,296 control chromosomes in the GnomAD database, including 306 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 0.060 (306 hom., cov: 33)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVT1	NR_003367.3	n.1213-32959C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000651587.1	n.913-32959C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9067 AN: 152178 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0596 AC: 9079 AN: 152296 Hom.: 306 Cov.: 33 AF XY: 0.0601 AC XY: 4474 AN XY: 74472

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.0714

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0703 Hom.: 138

Bravo AF: 0.0552

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13249999; hg19: chr8-129049447;