ENST00000650846.1:n.544+5063C>G

Variant names:

• chr8-128157880-C-G
• rs2608029
• ENST00000650846.1:n.544+5063C>G

Variant summary

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

The ENST00000650846.1(PVT1):​n.544+5063C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,908 control chromosomes in the GnomAD database, including 11,714 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 0.38 (11714 hom., cov: 31)
• Consequence: PVT1 ENST00000650846.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 15 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]

ENSG00000309955 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902020	XR_007061107.1	n.1904+2461C>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000650846.1	n.544+5063C>G		intron_variant	Intron 3 of 3
PVT1	ENST00000651587.1	n.1772+2461C>G		intron_variant	Intron 9 of 10
PVT1	ENST00000844540.1	n.1009+5063C>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57032 AN: 151790 Hom.: 11698 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.376 AC: 57081 AN: 151908 Hom.: 11714 Cov.: 31 AF XY: 0.385 AC XY: 28570 AN XY: 74238

African (AFR) AF: 0.320 AC: 13235 AN: 41390

American (AMR) AF: 0.453 AC: 6918 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4463 AN: 5164

South Asian (SAS) AF: 0.629 AC: 3023 AN: 4804

European-Finnish (FIN) AF: 0.324 AC: 3411 AN: 10538

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23223 AN: 67964

Other (OTH) AF: 0.407 AC: 855 AN: 2102

Alfa AF: 0.339 Hom.: 1148

Bravo AF: 0.384

Asia WGS AF: 0.713 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.29
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs2608029; hg19: chr8-129170126;