8-128105690-A-G

Variant names:

• chr8-128105690-A-G
• rs2720672
• ENST00000651587.1:n.1251+9036A>G

Variant summary

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

The ENST00000651587.1(PVT1):​n.1251+9036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,200 control chromosomes in the GnomAD database, including 29,017 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 (29017 hom., cov: 34)
• Consequence: PVT1 ENST00000651587.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000651587.1	n.1251+9036A>G		intron_variant	Intron 6 of 10

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90667 AN: 152082 Hom.: 28957 Cov.: 34

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.596 AC: 90786 AN: 152200 Hom.: 29017 Cov.: 34 AF XY: 0.596 AC XY: 44391 AN XY: 74422

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.614

Alfa AF: 0.500 Hom.: 10928

Bravo AF: 0.626

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.063
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2720672; hg19: chr8-129117936;