rs1499368

Variant names:

• chr8-128082343-C-T
• rs1499368
• ENST00000667305.2:n.1289+12071C>T

Variant summary

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

The ENST00000513868.6(PVT1):​n.1084+12071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 152,254 control chromosomes in the GnomAD database, including 832 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 0.084 (832 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 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.1289+12071C>T		intron	N/A
	PVT1	NR_003367.4		n.1334+12071C>T		intron	N/A
	PVT1	NR_186119.1		n.2132-410C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.1289+12071C>T		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.1084+12071C>T		intron	N/A
	PVT1	ENST00000512617.7	TSL:3	n.695+11982C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12734 AN: 152136 Hom.: 826 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0837 AC: 12746 AN: 152254 Hom.: 832 Cov.: 32 AF XY: 0.0881 AC XY: 6558 AN XY: 74442

African (AFR) AF: 0.0391 AC: 1625 AN: 41552

American (AMR) AF: 0.215 AC: 3295 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 401 AN: 3472

East Asian (EAS) AF: 0.173 AC: 895 AN: 5188

South Asian (SAS) AF: 0.163 AC: 784 AN: 4814

European-Finnish (FIN) AF: 0.0455 AC: 483 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4878 AN: 68004

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.0848 Hom.: 1301

Bravo AF: 0.0975

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.76
PhyloP100		-1.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1499368;

hg19: chr8-129094589;