8-127996332-G-C

Variant names:

• chr8-127996332-G-C
• rs3815871
• ENST00000513868.6:n.971+7041G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513868.6(PVT1):​n.971+7041G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,000 control chromosomes in the GnomAD database, including 8,332 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 0.31 (8332 hom., cov: 28)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1221+7041G>C		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1387-229G>C		intron_variant	Intron 6 of 14
PVT1	NR_186120.1	n.1802+1104G>C		intron_variant	Intron 8 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.971+7041G>C		intron_variant	Intron 4 of 7	1
PVT1	ENST00000512617.7	n.331+7041G>C		intron_variant	Intron 2 of 5	3
PVT1	ENST00000517525.2	n.1085-229G>C		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46766 AN: 150882 Hom.: 8317 Cov.: 28

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.310 AC: 46804 AN: 151000 Hom.: 8332 Cov.: 28 AF XY: 0.315 AC XY: 23206 AN XY: 73626

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.347

Alfa AF: 0.193 Hom.: 447

Bravo AF: 0.314

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3815871; hg19: chr8-129008578;