rs4339604

Variant names:

• chr8-127853225-G-A
• rs4339604
• ENST00000667305.2:n.212-37364G>A

Variant summary

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

The ENST00000667305.2(PVT1):​n.212-37364G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,196 control chromosomes in the GnomAD database, including 621 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 0.085 (621 hom., cov: 32)
• Consequence: PVT1 ENST00000667305.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_190187.1	n.212-37364G>A		intron_variant	Intron 1 of 8	ENST00000667305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000667305.2	n.212-37364G>A		intron_variant	Intron 1 of 8		NR_190187.1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12896 AN: 152078 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0848 AC: 12902 AN: 152196 Hom.: 621 Cov.: 32 AF XY: 0.0837 AC XY: 6229 AN XY: 74400

African (AFR) AF: 0.0969 AC: 4023 AN: 41528

American (AMR) AF: 0.0818 AC: 1250 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0721 AC: 347 AN: 4816

European-Finnish (FIN) AF: 0.0534 AC: 566 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5786 AN: 67988

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0898 Hom.: 1370

Bravo AF: 0.0871

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs4339604; hg19: chr8-128865471;