8-127960475-A-G

Position:

• chr8-127960475-A-G

Variant summary

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

The NR_003367.3(PVT1):​n.781+20799A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,974 control chromosomes in the GnomAD database, including 6,841 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 0.29 (6841 hom., cov: 31)
• Consequence: PVT1 NR_003367.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVT1	NR_003367.3	n.781+20799A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000651587.1	n.783-28687A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43802 AN: 151856 Hom.: 6831 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.289 AC: 43852 AN: 151974 Hom.: 6841 Cov.: 31 AF XY: 0.291 AC XY: 21615 AN XY: 74290

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.316

Alfa AF: 0.308 Hom.: 1485

Bravo AF: 0.272

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	18
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9649959; hg19: chr8-128972721; COSMIC: COSV68680571;