rs2392885

Variant names:

• chr8-127990871-T-C
• rs2392885
• ENST00000513868.6:n.971+1580T>C

Variant summary

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

The ENST00000513868.6(PVT1):​n.971+1580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,940 control chromosomes in the GnomAD database, including 6,351 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 0.28 (6351 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1221+1580T>C		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1386+1580T>C		intron_variant	Intron 6 of 14
PVT1	NR_186120.1	n.1456+1580T>C		intron_variant	Intron 7 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.971+1580T>C		intron_variant	Intron 4 of 7	1
PVT1	ENST00000512617.7	n.331+1580T>C		intron_variant	Intron 2 of 5	3
PVT1	ENST00000517525.2	n.1084+1580T>C		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43228 AN: 151822 Hom.: 6351 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.285 AC: 43242 AN: 151940 Hom.: 6351 Cov.: 32 AF XY: 0.288 AC XY: 21354 AN XY: 74258

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.275

Alfa AF: 0.279 Hom.: 1564

Bravo AF: 0.274

Asia WGS AF: 0.379 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2392885; hg19: chr8-129003117;