8-127822157-C-T

Variant names:

• chr8-127822157-C-T
• rs4733789
• ENST00000521951.2:n.178+27423C>T

Variant summary

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

The ENST00000521951.2(PVT1):​n.178+27423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,064 control chromosomes in the GnomAD database, including 24,168 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 0.56 (24168 hom., cov: 33)
• Consequence: PVT1 ENST00000521951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.211+27423C>T		intron_variant	Intron 1 of 8
PVT1	NR_186119.1	n.211+27423C>T		intron_variant	Intron 1 of 14
PVT1	NR_186120.1	n.326+26149C>T		intron_variant	Intron 2 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000521951.2	n.178+27423C>T		intron_variant	Intron 1 of 2	1
PVT1	ENST00000523328.6	n.227+5273C>T		intron_variant	Intron 2 of 4	1
PVT1	ENST00000504719.8	n.208+27423C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84866 AN: 151946 Hom.: 24142 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.559 AC: 84938 AN: 152064 Hom.: 24168 Cov.: 33 AF XY: 0.564 AC XY: 41938 AN XY: 74342

African (AFR) AF: 0.479 AC: 19858 AN: 41446

American (AMR) AF: 0.684 AC: 10449 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2060 AN: 5188

South Asian (SAS) AF: 0.607 AC: 2928 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6128 AN: 10562

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40048 AN: 67982

Other (OTH) AF: 0.555 AC: 1172 AN: 2110

Alfa AF: 0.577 Hom.: 110957

Bravo AF: 0.558

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
DANN	Benign	0.82
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs4733789; hg19: chr8-128834403;