rs5029317

Positions:

• chr8-128114607-T-C

Variant summary

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

The ENST00000651587.1(PVT1):​n.1251+17953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,324 control chromosomes in the GnomAD database, including 855 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 0.091 (855 hom., cov: 33)
• Consequence: PVT1 ENST00000651587.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000651587.1	n.1251+17953T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13881 AN: 152208 Hom.: 852 Cov.: 33

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0926

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

GnomAD4 genome AF: 0.0912 AC: 13893 AN: 152324 Hom.: 855 Cov.: 33 AF XY: 0.0936 AC XY: 6971 AN XY: 74490

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.100 Hom.: 733

Bravo AF: 0.0937

Asia WGS AF: 0.104 AC: 363 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	0.26
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5029317; hg19: chr8-129126853;