8-127966610-A-C

Variant names:

• chr8-127966610-A-C
• rs755521
• ENST00000513868.6:n.541-17294A>C

Variant summary

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

The ENST00000513868.6(PVT1):​n.541-17294A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,238 control chromosomes in the GnomAD database, including 2,184 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 0.16 (2184 hom., cov: 32)
• Consequence: PVT1 ENST00000513868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVT1	NR_003367.4	n.791-17294A>C		intron_variant	Intron 3 of 8
PVT1	NR_186119.1	n.956-17294A>C		intron_variant	Intron 4 of 14
PVT1	NR_186120.1	n.906-15750A>C		intron_variant	Intron 4 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVT1	ENST00000513868.6	n.541-17294A>C		intron_variant	Intron 2 of 7	1
PVT1	ENST00000517525.2	n.955-22552A>C		intron_variant	Intron 4 of 5	3
PVT1	ENST00000517790.2	n.1274-22552A>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24253 AN: 152120 Hom.: 2177 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.160 AC: 24295 AN: 152238 Hom.: 2184 Cov.: 32 AF XY: 0.163 AC XY: 12151 AN XY: 74438

African (AFR) AF: 0.0858 AC: 3563 AN: 41546

American (AMR) AF: 0.195 AC: 2974 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 609 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5188

South Asian (SAS) AF: 0.294 AC: 1413 AN: 4814

European-Finnish (FIN) AF: 0.177 AC: 1876 AN: 10600

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12564 AN: 68010

Other (OTH) AF: 0.193 AC: 408 AN: 2114

Alfa AF: 0.175 Hom.: 9513

Bravo AF: 0.152

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.73
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs755521; hg19: chr8-128978856;