rs755520

Variant names:

• chr8-127966080-A-G
• rs755520
• ENST00000667305.2:n.791-23082A>G

Variant summary

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

The ENST00000667305.2(PVT1):​n.791-23082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,044 control chromosomes in the GnomAD database, including 11,979 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 0.39 (11979 hom., cov: 32)
• Consequence: PVT1 ENST00000667305.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000667305.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	NR_190187.1	MANE Select	n.791-23082A>G		intron	N/A
	PVT1	NR_003367.4		n.791-17824A>G		intron	N/A
	PVT1	NR_186119.1		n.956-17824A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.791-23082A>G		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.541-17824A>G		intron	N/A
	PVT1	ENST00000517525.2	TSL:3	n.955-23082A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59160 AN: 151926 Hom.: 11987 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.389 AC: 59167 AN: 152044 Hom.: 11979 Cov.: 32 AF XY: 0.397 AC XY: 29495 AN XY: 74310

African (AFR) AF: 0.306 AC: 12683 AN: 41454

American (AMR) AF: 0.470 AC: 7188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3089 AN: 5174

South Asian (SAS) AF: 0.471 AC: 2267 AN: 4810

European-Finnish (FIN) AF: 0.441 AC: 4657 AN: 10568

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26457 AN: 67974

Other (OTH) AF: 0.388 AC: 818 AN: 2110

Alfa AF: 0.394 Hom.: 41593

Bravo AF: 0.390

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs755520; hg19: chr8-128978326;