ENST00000513868.6:n.972-10245G>A

Variant names:

• chr8-128059915-G-A
• rs2648875
• ENST00000513868.6:n.972-10245G>A

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-10245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,958 control chromosomes in the GnomAD database, including 9,586 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 0.34 (9586 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 30 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1222-10245G>A		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1841-10245G>A		intron_variant	Intron 10 of 14
PVT1	NR_186120.1	n.2219-10245G>A		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.972-10245G>A		intron_variant	Intron 4 of 7	1
PVT1	ENST00000512617.7	n.494-10245G>A		intron_variant	Intron 3 of 5	3
PVT1	ENST00000521600.5	n.238-10245G>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51107 AN: 151840 Hom.: 9556 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.337 AC: 51185 AN: 151958 Hom.: 9586 Cov.: 32 AF XY: 0.345 AC XY: 25629 AN XY: 74274

African (AFR) AF: 0.450 AC: 18634 AN: 41418

American (AMR) AF: 0.413 AC: 6307 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3464

East Asian (EAS) AF: 0.587 AC: 3031 AN: 5166

South Asian (SAS) AF: 0.503 AC: 2419 AN: 4810

European-Finnish (FIN) AF: 0.282 AC: 2986 AN: 10570

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15927 AN: 67958

Other (OTH) AF: 0.331 AC: 698 AN: 2108

Alfa AF: 0.278 Hom.: 21020

Bravo AF: 0.349

Asia WGS AF: 0.551 AC: 1915 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	0.49
DANN	Benign	0.71
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2648875; hg19: chr8-129072161;