chr8-127828030-T-C

Variant names:

• chr8-127828030-T-C
• rs4733792
• ENST00000521951.2:n.178+33296T>C

Variant summary

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

The ENST00000521951.2(PVT1):​n.178+33296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,084 control chromosomes in the GnomAD database, including 36,211 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 0.68 (36211 hom., cov: 32)
• Consequence: PVT1 ENST00000521951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.211+33296T>C		intron_variant	Intron 1 of 8
PVT1	NR_186119.1	n.212-27125T>C		intron_variant	Intron 1 of 14
PVT1	NR_186120.1	n.326+32022T>C		intron_variant	Intron 2 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000521951.2	n.178+33296T>C		intron_variant	Intron 1 of 2	1
PVT1	ENST00000523328.6	n.227+11146T>C		intron_variant	Intron 2 of 4	1
PVT1	ENST00000504719.8	n.209-27125T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102845 AN: 151966 Hom.: 36153 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.677 AC: 102965 AN: 152084 Hom.: 36211 Cov.: 32 AF XY: 0.679 AC XY: 50448 AN XY: 74332

African (AFR) AF: 0.870 AC: 36114 AN: 41532

American (AMR) AF: 0.728 AC: 11123 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3466

East Asian (EAS) AF: 0.518 AC: 2668 AN: 5152

South Asian (SAS) AF: 0.637 AC: 3055 AN: 4798

European-Finnish (FIN) AF: 0.578 AC: 6105 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40237 AN: 67982

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.607 Hom.: 79568

Bravo AF: 0.692

Asia WGS AF: 0.621 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.44
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs4733792; hg19: chr8-128840276;