8-128008933-G-A

Variant names:

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

Variant summary

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

The ENST00000667305.2(PVT1):​n.921-657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 522,284 control chromosomes in the GnomAD database, including 101,439 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 0.65 (32173 hom., cov: 32)
  • Exomes 𝑓: 0.61 (69266 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

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>A		intron	N/A
	MIR1206	NR_031611.1		n.36G>A		non_coding_transcript_exon	Exon 1 of 1
	PVT1	NR_003367.4		n.1221+19642G>A		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98203 AN: 151886 Hom.: 32136 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.624

GnomAD2 exomes AF: 0.626 AC: 154054 AN: 246132 AF XY: 0.616

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.697

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.710

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.608 AC: 225148 AN: 370280 Hom.: 69266 Cov.: 0 AF XY: 0.599 AC XY: 126400 AN XY: 211028

African (AFR) AF: 0.725 AC: 7551 AN: 10418

American (AMR) AF: 0.695 AC: 25144 AN: 36194

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 6919 AN: 11444

East Asian (EAS) AF: 0.711 AC: 9275 AN: 13040

South Asian (SAS) AF: 0.532 AC: 34839 AN: 65462

European-Finnish (FIN) AF: 0.644 AC: 20416 AN: 31722

Middle Eastern (MID) AF: 0.526 AC: 1472 AN: 2796

European-Non Finnish (NFE) AF: 0.600 AC: 109864 AN: 183080

Other (OTH) AF: 0.600 AC: 9668 AN: 16124

GnomAD4 genome AF: 0.647 AC: 98287 AN: 152004 Hom.: 32173 Cov.: 32 AF XY: 0.649 AC XY: 48231 AN XY: 74298

African (AFR) AF: 0.729 AC: 30206 AN: 41458

American (AMR) AF: 0.669 AC: 10214 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2027 AN: 3466

East Asian (EAS) AF: 0.713 AC: 3687 AN: 5168

South Asian (SAS) AF: 0.554 AC: 2664 AN: 4812

European-Finnish (FIN) AF: 0.638 AC: 6732 AN: 10554

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40650 AN: 67950

Other (OTH) AF: 0.619 AC: 1309 AN: 2114

Alfa AF: 0.622 Hom.: 60380

Bravo AF: 0.657

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.76
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;