chr8-127806062-A-G

Variant names:

• chr8-127806062-A-G
• rs7841347
• ENST00000667305.2:n.211+11328A>G

Variant summary

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

The ENST00000667305.2(PVT1):​n.211+11328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,060 control chromosomes in the GnomAD database, including 18,211 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 0.48 (18211 hom., cov: 32)
• Consequence: PVT1 ENST00000667305.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 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.211+11328A>G		intron	N/A
	PVT1	NR_003367.4		n.211+11328A>G		intron	N/A
	PVT1	NR_186119.1		n.211+11328A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVT1	ENST00000667305.2	MANE Select	n.211+11328A>G		intron	N/A
	PVT1	ENST00000521951.2	TSL:1	n.178+11328A>G		intron	N/A
	PVT1	ENST00000523328.6	TSL:1	n.171-10766A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73532 AN: 151942 Hom.: 18181 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.484 AC: 73616 AN: 152060 Hom.: 18211 Cov.: 32 AF XY: 0.478 AC XY: 35511 AN XY: 74328

African (AFR) AF: 0.538 AC: 22303 AN: 41474

American (AMR) AF: 0.439 AC: 6708 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1837 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1307 AN: 5180

South Asian (SAS) AF: 0.403 AC: 1942 AN: 4822

European-Finnish (FIN) AF: 0.446 AC: 4706 AN: 10540

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33149 AN: 67976

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.485 Hom.: 41398

Bravo AF: 0.487

Asia WGS AF: 0.384 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs7841347; hg19: chr8-128818308;