rs755520

chr8-127966080-A-G

Variant summary

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

The NR_003367.3(PVT1):n.782-17824A>G 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 0.389 in 152,044 control chromosomes in the GnomAD database, including 11,979 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 0.39 (11979 hom., cov: 32)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVT1	NR_003367.3	n.782-17824A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVT1	ENST00000651587.1	n.783-23082A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59160 AN: 151926 Hom.: 11987 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.389 AC: 59167 AN: 152044 Hom.: 11979 Cov.: 32 AF XY: 0.397 AC XY: 29495 AN XY: 74310

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.388

Alfa AF: 0.398 Hom.: 18823

Bravo AF: 0.390

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755520; hg19: chr8-128978326;