8-127802783-T-C

Variant names:

• chr8-127802783-T-C
• rs4410871
• ENST00000667305.2:n.211+8049T>C

Variant summary

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

The ENST00000667305.2(PVT1):​n.211+8049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,066 control chromosomes in the GnomAD database, including 41,405 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 0.73 (41405 hom., cov: 31)
• Consequence: PVT1 ENST00000667305.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 65 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_190187.1	n.211+8049T>C		intron_variant	Intron 1 of 8	ENST00000667305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000667305.2	n.211+8049T>C		intron_variant	Intron 1 of 8		NR_190187.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111561 AN: 151948 Hom.: 41347 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.734 AC: 111675 AN: 152066 Hom.: 41405 Cov.: 31 AF XY: 0.731 AC XY: 54325 AN XY: 74340

African (AFR) AF: 0.828 AC: 34346 AN: 41496

American (AMR) AF: 0.610 AC: 9314 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2327 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3258 AN: 5146

South Asian (SAS) AF: 0.722 AC: 3478 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7644 AN: 10558

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48955 AN: 67980

Other (OTH) AF: 0.704 AC: 1483 AN: 2108

Alfa AF: 0.723 Hom.: 144818

Bravo AF: 0.727

Asia WGS AF: 0.720 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.8
DANN	Benign	0.65
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs4410871; hg19: chr8-128815029;