rs10808565

Variant names:

• chr8-127995166-C-T
• rs10808565
• ENST00000513868.6:n.971+5875C>T

Variant summary

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

The ENST00000513868.6(PVT1):​n.971+5875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,042 control chromosomes in the GnomAD database, including 8,661 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 0.31 (8661 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• Publications: 5 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]

ENSG00000310067 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_186120.1	n.1740C>T		non_coding_transcript_exon_variant	Exon 8 of 15
PVT1	NR_186124.1	n.1204C>T		non_coding_transcript_exon_variant	Exon 5 of 13
PVT1	NR_186127.1	n.1204C>T		non_coding_transcript_exon_variant	Exon 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.971+5875C>T		intron_variant	Intron 4 of 7	1
PVT1	ENST00000653497.1	n.218C>T		non_coding_transcript_exon_variant	Exon 1 of 7
PVT1	ENST00000665721.2	n.1169C>T		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47822 AN: 151924 Hom.: 8647 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.315 AC: 47859 AN: 152042 Hom.: 8661 Cov.: 32 AF XY: 0.321 AC XY: 23824 AN XY: 74314

African (AFR) AF: 0.152 AC: 6301 AN: 41508

American (AMR) AF: 0.516 AC: 7884 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1132 AN: 5160

South Asian (SAS) AF: 0.444 AC: 2139 AN: 4814

European-Finnish (FIN) AF: 0.333 AC: 3514 AN: 10562

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24409 AN: 67950

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.334 Hom.: 3050

Bravo AF: 0.318

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.34
PhyloP100		-3.5

Splicing

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

Other links and lift over

dbSNP: rs10808565; hg19: chr8-129007412;