ENST00000513868.6:n.371+16953G>A

Variant names:

• chr8-127907951-G-A
• rs16902460
• ENST00000667305.2:n.621+16953G>A

Variant summary

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

The ENST00000513868.6(PVT1):​n.371+16953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 152,214 control chromosomes in the GnomAD database, including 31 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 0.0078 (31 hom., cov: 31)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513868.6. 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.621+16953G>A		intron	N/A
	PVT1	NR_003367.4		n.621+16953G>A		intron	N/A
	PVT1	NR_186119.1		n.786+16953G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.621+16953G>A		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.371+16953G>A		intron	N/A
	PVT1	ENST00000521951.2	TSL:1	n.588+16953G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00780 AC: 1186 AN: 152096 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0979

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00908

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

GnomAD4 genome AF: 0.00779 AC: 1185 AN: 152214 Hom.: 31 Cov.: 31 AF XY: 0.00832 AC XY: 619 AN XY: 74422

African (AFR) AF: 0.0108 AC: 447 AN: 41538

American (AMR) AF: 0.00275 AC: 42 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.0979 AC: 506 AN: 5166

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 68006

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.00812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.60
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs16902460; hg19: chr8-128920197;