rs6470600

Positions:

• chr8-128030799-G-A

Variant summary

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

The NR_003367.3(PVT1):​n.1213-39361G>A 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 0.144 in 152,136 control chromosomes in the GnomAD database, including 3,580 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 0.14 (3580 hom., cov: 32)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVT1	NR_003367.3	n.1213-39361G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000651587.1	n.913-39361G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21859 AN: 152018 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.144 AC: 21939 AN: 152136 Hom.: 3580 Cov.: 32 AF XY: 0.142 AC XY: 10563 AN XY: 74388

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0783

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0882 Hom.: 326

Bravo AF: 0.156

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6470600; hg19: chr8-129043045;