rs10283090

Variant names:

• chr8-127998344-C-A
• rs10283090
• ENST00000513868.6:n.971+9053C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513868.6(PVT1):​n.971+9053C>A variant causes a intron 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 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PVT1	NR_186119.1	n.1569C>A		non_coding_transcript_exon_variant	Exon 8 of 15
PVT1	NR_186120.1	n.1947C>A		non_coding_transcript_exon_variant	Exon 9 of 15
PVT1	NR_186123.1	n.1735C>A		non_coding_transcript_exon_variant	Exon 9 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.971+9053C>A		intron_variant	Intron 4 of 7	1
PVT1	ENST00000522875.5	n.214C>A		non_coding_transcript_exon_variant	Exon 3 of 8	5
PVT1	ENST00000656999.1	n.316C>A		non_coding_transcript_exon_variant	Exon 1 of 6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0432 AC: 1793 AN: 41546

American (AMR) AF: 0.107 AC: 1631 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.116 AC: 602 AN: 5182

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1726 AN: 10570

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12056 AN: 67988

Other (OTH) AF: 0.122 AC: 258 AN: 2110

Alfa AF: 0.164 Hom.: 1027

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
PhyloP100		-0.033

Splicing

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

Other links and lift over

dbSNP: rs10283090; hg19: chr8-129010590;