rs2019960

chr8-128180025-T-C

Variant summary

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

The ENST00000651587.1(PVT1):n.1899-6531T>C 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 0.266 in 152,058 control chromosomes in the GnomAD database, including 6,192 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 0.27 (6192 hom., cov: 32)
• Consequence: PVT1 ENST00000651587.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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]

LOC124902020 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902020	XR_007061107.1	n.1905-6531T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVT1	ENST00000651587.1	n.1899-6531T>C		intron_variant, non_coding_transcript_variant
PVT1	ENST00000650846.1	n.545-6531T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40329 AN: 151940 Hom.: 6185 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.266 AC: 40376 AN: 152058 Hom.: 6192 Cov.: 32 AF XY: 0.261 AC XY: 19410 AN XY: 74340

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.251

Alfa AF: 0.215 Hom.: 8624

Bravo AF: 0.281

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	7.1
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2019960; hg19: chr8-129192271;