chr8-128008933-G-C

Variant names:

• chr8-128008933-G-C
• rs2114358
• ENST00000667305.2:n.921-657G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000667305.2(PVT1):​n.921-657G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PVT1 ENST00000667305.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 43 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]

MIR1206 (HGNC:35272): (microRNA 1206) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000667305.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	NR_190187.1	MANE Select	n.921-657G>C		intron	N/A
	MIR1206	NR_031611.1		n.36G>C		non_coding_transcript_exon	Exon 1 of 1
	PVT1	NR_003367.4		n.1221+19642G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.921-657G>C		intron	N/A
	PVT1	ENST00000513868.6	TSL:1	n.971+19642G>C		intron	N/A
	MIR1206	ENST00000637127.1	TSL:6	n.36G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 371950 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 211966

African (AFR) AF: 0.00 AC: 0 AN: 10438

American (AMR) AF: 0.00 AC: 0 AN: 36248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11478

East Asian (EAS) AF: 0.00 AC: 0 AN: 13070

South Asian (SAS) AF: 0.00 AC: 0 AN: 65772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2808

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 184092

Other (OTH) AF: 0.00 AC: 0 AN: 16220

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 60380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs2114358; hg19: chr8-129021179;