8-127977046-C-T

Variant names:

• chr8-127977046-C-T
• rs4733809
• ENST00000667305.2:n.791-12116C>T

Variant summary

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

The ENST00000513868.6(PVT1):​n.541-6858C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,024 control chromosomes in the GnomAD database, including 24,285 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 0.55 (24285 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 6 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513868.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	NR_190187.1	MANE Select	n.791-12116C>T		intron	N/A
	PVT1	NR_003367.4		n.791-6858C>T		intron	N/A
	PVT1	NR_186119.1		n.956-6858C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.791-12116C>T		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.541-6858C>T		intron	N/A
	PVT1	ENST00000517525.2	TSL:3	n.955-12116C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83966 AN: 151906 Hom.: 24258 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.553 AC: 84033 AN: 152024 Hom.: 24285 Cov.: 32 AF XY: 0.564 AC XY: 41926 AN XY: 74320

African (AFR) AF: 0.388 AC: 16088 AN: 41432

American (AMR) AF: 0.674 AC: 10305 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2316 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3717 AN: 5172

South Asian (SAS) AF: 0.805 AC: 3884 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6470 AN: 10564

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39211 AN: 67954

Other (OTH) AF: 0.597 AC: 1259 AN: 2110

Alfa AF: 0.586 Hom.: 36867

Bravo AF: 0.547

Asia WGS AF: 0.705 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.82
PhyloP100		0.82

Splicing

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

Other links and lift over

dbSNP: rs4733809; hg19: chr8-128989292;