rs13249999

Variant names:

• chr8-128037201-C-T
• rs13249999
• ENST00000513868.6:n.972-32959C>T

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-32959C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,296 control chromosomes in the GnomAD database, including 306 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 0.060 (306 hom., cov: 33)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1222-32959C>T		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1840+26757C>T		intron_variant	Intron 10 of 14
PVT1	NR_186120.1	n.2218+26757C>T		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.972-32959C>T		intron_variant	Intron 4 of 7	1
PVT1	ENST00000512617.7	n.332-11247C>T		intron_variant	Intron 2 of 5	3
PVT1	ENST00000521600.5	n.76-11247C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9067 AN: 152178 Hom.: 305 Cov.: 33

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0596 AC: 9079 AN: 152296 Hom.: 306 Cov.: 33 AF XY: 0.0601 AC XY: 4474 AN XY: 74472

African (AFR) AF: 0.0390 AC: 1621 AN: 41586

American (AMR) AF: 0.0413 AC: 632 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5182

South Asian (SAS) AF: 0.0650 AC: 314 AN: 4828

European-Finnish (FIN) AF: 0.0714 AC: 758 AN: 10614

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5094 AN: 68002

Other (OTH) AF: 0.0540 AC: 114 AN: 2110

Alfa AF: 0.0664 Hom.: 302

Bravo AF: 0.0552

Asia WGS AF: 0.0550 AC: 193 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	0.77
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13249999; hg19: chr8-129049447;