rs2648862

Variant names:

• chr8-128049539-C-A
• rs2648862
• ENST00000513868.6:n.972-20621C>A

Variant summary

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

The ENST00000513868.6(PVT1):​n.972-20621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 152,228 control chromosomes in the GnomAD database, including 171 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 0.031 (171 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 7 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.1222-20621C>A		intron_variant	Intron 5 of 8
PVT1	NR_186119.1	n.1841-20621C>A		intron_variant	Intron 10 of 14
PVT1	NR_186120.1	n.2219-20621C>A		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.972-20621C>A		intron_variant	Intron 4 of 7	1
PVT1	ENST00000522414.2	n.152C>A		non_coding_transcript_exon_variant	Exon 1 of 4	2
PVT1	ENST00000652728.2	n.400C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4748 AN: 152110 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0312 AC: 4751 AN: 152228 Hom.: 171 Cov.: 32 AF XY: 0.0352 AC XY: 2617 AN XY: 74410

African (AFR) AF: 0.0199 AC: 826 AN: 41560

American (AMR) AF: 0.0648 AC: 991 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.185 AC: 955 AN: 5162

South Asian (SAS) AF: 0.0620 AC: 298 AN: 4810

European-Finnish (FIN) AF: 0.0464 AC: 492 AN: 10604

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0140 AC: 953 AN: 68006

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.0216 Hom.: 185

Bravo AF: 0.0326

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.82
PhyloP100		-0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2648862; hg19: chr8-129061785;