rs1365371

chr8-127936977-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.613-2531A>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 0.662 in 152,078 control chromosomes in the GnomAD database, including 33,793 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 0.66 (33793 hom., cov: 33)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVT1	NR_003367.3	n.613-2531A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVT1	ENST00000651587.1	n.782+45979A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100663 AN: 151960 Hom.: 33767 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.662 AC: 100733 AN: 152078 Hom.: 33793 Cov.: 33 AF XY: 0.661 AC XY: 49112 AN XY: 74336

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.697

Alfa AF: 0.662 Hom.: 4968

Bravo AF: 0.643

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.60
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1365371; hg19: chr8-128949223;