rs6470600

Variant names:

• chr8-128030799-G-A
• rs6470600
• ENST00000513868.6:n.972-39361G>A

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-39361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,136 control chromosomes in the GnomAD database, including 3,580 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 0.14 (3580 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1222-39361G>A		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1840+20355G>A		intron_variant	Intron 10 of 14
PVT1	NR_186120.1	n.2218+20355G>A		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.972-39361G>A		intron_variant	Intron 4 of 7	1
PVT1	ENST00000512617.7	n.332-17649G>A		intron_variant	Intron 2 of 5	3
PVT1	ENST00000521600.5	n.76-17649G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21859 AN: 152018 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.144 AC: 21939 AN: 152136 Hom.: 3580 Cov.: 32 AF XY: 0.142 AC XY: 10563 AN XY: 74388

African (AFR) AF: 0.405 AC: 16796 AN: 41478

American (AMR) AF: 0.0730 AC: 1116 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.142 AC: 736 AN: 5178

South Asian (SAS) AF: 0.0783 AC: 377 AN: 4812

European-Finnish (FIN) AF: 0.0472 AC: 499 AN: 10580

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1883 AN: 68006

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.0968 Hom.: 380

Bravo AF: 0.156

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DANN	Benign	0.56
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs6470600; hg19: chr8-129043045;