chr8-128140986-T-C

Variant names:

• chr8-128140986-T-C
• rs2608038
• ENST00000650846.1:n.277-6876T>C

Variant summary

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

The ENST00000650846.1(PVT1):​n.277-6876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,224 control chromosomes in the GnomAD database, including 1,682 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 0.13 (1682 hom., cov: 32)
• Consequence: PVT1 ENST00000650846.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 4 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]

ENSG00000310100 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650846.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000650846.1		n.277-6876T>C		intron	N/A
	PVT1	ENST00000651587.1		n.1252-6876T>C		intron	N/A
	PVT1	ENST00000844540.1		n.869-11691T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20361 AN: 152106 Hom.: 1686 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.134 AC: 20363 AN: 152224 Hom.: 1682 Cov.: 32 AF XY: 0.138 AC XY: 10273 AN XY: 74430

African (AFR) AF: 0.101 AC: 4207 AN: 41532

American (AMR) AF: 0.182 AC: 2788 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 284 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2176 AN: 5174

South Asian (SAS) AF: 0.204 AC: 984 AN: 4814

European-Finnish (FIN) AF: 0.133 AC: 1410 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 7998 AN: 68018

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.125 Hom.: 336

Bravo AF: 0.139

Asia WGS AF: 0.319 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs2608038; hg19: chr8-129153232; COSMIC: COSV107189817;