8-128063586-T-C

Variant names:

• chr8-128063586-T-C
• rs2608053
• ENST00000667305.2:n.1177-6574T>C

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-6574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,958 control chromosomes in the GnomAD database, including 19,985 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 0.51 (19985 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 34 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 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.1177-6574T>C		intron	N/A
	PVT1	NR_003367.4		n.1222-6574T>C		intron	N/A
	PVT1	NR_186119.1		n.1841-6574T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.1177-6574T>C		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.972-6574T>C		intron	N/A
	PVT1	ENST00000512617.7	TSL:3	n.494-6574T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77063 AN: 151840 Hom.: 19965 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.508 AC: 77119 AN: 151958 Hom.: 19985 Cov.: 32 AF XY: 0.514 AC XY: 38206 AN XY: 74282

African (AFR) AF: 0.411 AC: 17022 AN: 41428

American (AMR) AF: 0.554 AC: 8472 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1881 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3829 AN: 5170

South Asian (SAS) AF: 0.567 AC: 2720 AN: 4796

European-Finnish (FIN) AF: 0.581 AC: 6129 AN: 10556

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35354 AN: 67934

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.530 Hom.: 47218

Bravo AF: 0.502

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.69
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs2608053; hg19: chr8-129075832;