chr8-127980241-T-C

Variant names:

• chr8-127980241-T-C
• rs11993333
• ENST00000513868.6:n.541-3663T>C

Variant summary

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

The ENST00000513868.6(PVT1):​n.541-3663T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,928 control chromosomes in the GnomAD database, including 18,346 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 0.47 (18346 hom., cov: 31)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 (SAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.791-3663T>C		intron_variant	Intron 3 of 8
PVT1	NR_186119.1	n.956-3663T>C		intron_variant	Intron 4 of 14
PVT1	NR_186120.1	n.906-2119T>C		intron_variant	Intron 4 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.541-3663T>C		intron_variant	Intron 2 of 7	1
PVT1	ENST00000517525.2	n.955-8921T>C		intron_variant	Intron 4 of 5	3
PVT1	ENST00000517790.2	n.1274-8921T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71968 AN: 151810 Hom.: 18338 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.474 AC: 71995 AN: 151928 Hom.: 18346 Cov.: 31 AF XY: 0.487 AC XY: 36158 AN XY: 74260

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.517

Alfa AF: 0.507 Hom.: 21922

Bravo AF: 0.466

Asia WGS AF: 0.609 AC: 2118 AN: 3478

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	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11993333; hg19: chr8-128992487;