8-128173226-C-A

Variant names:

• chr8-128173226-C-A
• rs2936594
• ENST00000650846.1:n.545-13330C>A

Variant summary

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

The ENST00000650846.1(PVT1):​n.545-13330C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,126 control chromosomes in the GnomAD database, including 36,112 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 0.67 (36112 hom., cov: 32)
• Consequence: PVT1 ENST00000650846.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 3 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]

LOC124902020 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902020	XR_007061107.1	n.1905-13330C>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000650846.1	n.545-13330C>A		intron_variant	Intron 3 of 3
PVT1	ENST00000651587.1	n.1898+12345C>A		intron_variant	Intron 10 of 10
PVT1	ENST00000844540.1	n.1010-13330C>A		intron_variant	Intron 5 of 5
PVT1	ENST00000844775.1	n.597-13330C>A		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102295 AN: 152006 Hom.: 36053 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.673 AC: 102414 AN: 152126 Hom.: 36112 Cov.: 32 AF XY: 0.676 AC XY: 50299 AN XY: 74366

African (AFR) AF: 0.841 AC: 34947 AN: 41534

American (AMR) AF: 0.755 AC: 11536 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2258 AN: 3470

East Asian (EAS) AF: 0.968 AC: 5014 AN: 5182

South Asian (SAS) AF: 0.757 AC: 3652 AN: 4822

European-Finnish (FIN) AF: 0.510 AC: 5383 AN: 10550

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37541 AN: 67980

Other (OTH) AF: 0.689 AC: 1453 AN: 2108

Alfa AF: 0.632 Hom.: 4784

Bravo AF: 0.701

Asia WGS AF: 0.873 AC: 3033 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.24
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs2936594; hg19: chr8-129185472;