8-128033045-C-G

Variant names:

• chr8-128033045-C-G
• rs10505506
• ENST00000667305.2:n.1176+22601C>G

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-37115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,102 control chromosomes in the GnomAD database, including 8,438 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 0.32 (8438 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 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.1176+22601C>G		intron	N/A
	PVT1	NR_003367.4		n.1222-37115C>G		intron	N/A
	PVT1	NR_186119.1		n.1840+22601C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.1176+22601C>G		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.972-37115C>G		intron	N/A
	PVT1	ENST00000512617.7	TSL:3	n.332-15403C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48395 AN: 151984 Hom.: 8423 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.318 AC: 48435 AN: 152102 Hom.: 8438 Cov.: 32 AF XY: 0.328 AC XY: 24415 AN XY: 74350

African (AFR) AF: 0.200 AC: 8297 AN: 41504

American (AMR) AF: 0.470 AC: 7186 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2326 AN: 5164

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4820

European-Finnish (FIN) AF: 0.322 AC: 3402 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22266 AN: 67978

Other (OTH) AF: 0.339 AC: 717 AN: 2114

Alfa AF: 0.185 Hom.: 406

Bravo AF: 0.324

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.68
PhyloP100		0.095
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: rs10505506; hg19: chr8-129045291;