rs10283090

chr8-127998344-C-A

Variant summary

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

The NR_003367.3(PVT1):n.1212+9053C>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 0.125 in 152,182 control chromosomes in the GnomAD database, including 1,538 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 0.13 (1538 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVT1	NR_003367.3	n.1212+9053C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVT1	ENST00000651587.1	n.912+9053C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19049 AN: 152064 Hom.: 1539 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.124

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.125 AC: 19041 AN: 152182 Hom.: 1538 Cov.: 32 AF XY: 0.123 AC XY: 9187 AN XY: 74390

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0691

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.122

Alfa AF: 0.160 Hom.: 606

Bravo AF: 0.121

Asia WGS AF: 0.0720 AC: 249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.7
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10283090; hg19: chr8-129010590;