rs9649959

Variant names:

• chr8-127960475-A-G
• rs9649959
• ENST00000513868.6:n.540+20799A>G

Variant summary

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

The ENST00000513868.6(PVT1):​n.540+20799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,974 control chromosomes in the GnomAD database, including 6,841 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 0.29 (6841 hom., cov: 31)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 8 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]

MIR1205 (HGNC:35271): (microRNA 1205) 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.790+20799A>G		intron_variant	Intron 3 of 8
PVT1	NR_186119.1	n.955+20799A>G		intron_variant	Intron 4 of 14
PVT1	NR_186120.1	n.905+20799A>G		intron_variant	Intron 4 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.540+20799A>G		intron_variant	Intron 2 of 7	1
PVT1	ENST00000844666.1	n.26A>G		non_coding_transcript_exon_variant	Exon 1 of 5
PVT1	ENST00000844780.1	n.26A>G		non_coding_transcript_exon_variant	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43802 AN: 151856 Hom.: 6831 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.289 AC: 43852 AN: 151974 Hom.: 6841 Cov.: 31 AF XY: 0.291 AC XY: 21615 AN XY: 74290

African (AFR) AF: 0.199 AC: 8234 AN: 41434

American (AMR) AF: 0.281 AC: 4291 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3472

East Asian (EAS) AF: 0.132 AC: 682 AN: 5160

South Asian (SAS) AF: 0.316 AC: 1513 AN: 4794

European-Finnish (FIN) AF: 0.397 AC: 4197 AN: 10566

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22872 AN: 67938

Other (OTH) AF: 0.316 AC: 667 AN: 2112

Alfa AF: 0.302 Hom.: 2647

Bravo AF: 0.272

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	18
DANN	Benign	0.66
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs9649959; hg19: chr8-128972721; COSMIC: COSV68680571;