8-127796593-T-C

Variant names:

• chr8-127796593-T-C
• rs10956390
• ENST00000521951.2:n.178+1859T>C

Variant summary

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

The ENST00000521951.2(PVT1):​n.178+1859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,992 control chromosomes in the GnomAD database, including 27,553 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 0.60 (27553 hom., cov: 31)
• Consequence: PVT1 ENST00000521951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 7 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 (SAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.211+1859T>C		intron_variant	Intron 1 of 8
PVT1	NR_186119.1	n.211+1859T>C		intron_variant	Intron 1 of 14
PVT1	NR_186120.1	n.326+585T>C		intron_variant	Intron 2 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000521951.2	n.178+1859T>C		intron_variant	Intron 1 of 2	1
PVT1	ENST00000523328.6	n.170+1859T>C		intron_variant	Intron 1 of 4	1
PVT1	ENST00000504719.8	n.208+1859T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91019 AN: 151874 Hom.: 27526 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.599 AC: 91097 AN: 151992 Hom.: 27553 Cov.: 31 AF XY: 0.597 AC XY: 44335 AN XY: 74294

African (AFR) AF: 0.627 AC: 25975 AN: 41448

American (AMR) AF: 0.522 AC: 7966 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1980 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2635 AN: 5166

South Asian (SAS) AF: 0.687 AC: 3309 AN: 4820

European-Finnish (FIN) AF: 0.587 AC: 6194 AN: 10554

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.605 AC: 41140 AN: 67944

Other (OTH) AF: 0.563 AC: 1188 AN: 2112

Alfa AF: 0.604 Hom.: 28308

Bravo AF: 0.592

Asia WGS AF: 0.635 AC: 2211 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	1.1
DANN	Benign	0.43
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs10956390; hg19: chr8-128808839; COSMIC: COSV68600068;