rs1365371

Variant names:

• chr8-127936977-A-G
• rs1365371
• ENST00000513868.6:n.372-2531A>G

Variant summary

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

The ENST00000513868.6(PVT1):​n.372-2531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,078 control chromosomes in the GnomAD database, including 33,793 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 0.66 (33793 hom., cov: 33)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.622-2531A>G		intron_variant	Intron 2 of 8
PVT1	NR_186119.1	n.787-2531A>G		intron_variant	Intron 3 of 14
PVT1	NR_186120.1	n.737-2531A>G		intron_variant	Intron 3 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.372-2531A>G		intron_variant	Intron 1 of 7	1
PVT1	ENST00000521951.2	n.589-2531A>G		intron_variant	Intron 2 of 2	1
PVT1	ENST00000517525.2	n.786-2531A>G		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100663 AN: 151960 Hom.: 33767 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.662 AC: 100733 AN: 152078 Hom.: 33793 Cov.: 33 AF XY: 0.661 AC XY: 49112 AN XY: 74336

African (AFR) AF: 0.600 AC: 24860 AN: 41464

American (AMR) AF: 0.564 AC: 8619 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2439 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3282 AN: 5144

South Asian (SAS) AF: 0.658 AC: 3172 AN: 4824

European-Finnish (FIN) AF: 0.749 AC: 7929 AN: 10588

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48085 AN: 67982

Other (OTH) AF: 0.697 AC: 1471 AN: 2110

Alfa AF: 0.662 Hom.: 4968

Bravo AF: 0.643

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.32
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs1365371; hg19: chr8-128949223;