8-127082911-A-G

Position:

• chr8-127082911-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_109833.1(PRNCR1):​n.3038A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,154 control chromosomes in the GnomAD database, including 5,804 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 0.25 (5804 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PRNCR1 NR_109833.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

Genes affected

PRNCR1 (HGNC:48942): (prostate cancer associated non-coding RNA 1)

CASC19 (HGNC:49476): (cancer susceptibility 19)

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRNCR1	NR_109833.1	n.3038A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRNCR1	ENST00000635449.1	n.3038A>G		non_coding_transcript_exon_variant	1/1
CASC19	ENST00000642100.1	n.418-3778T>C		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000645463.1	n.855+76293A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37761 AN: 152036 Hom.: 5797 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.248 AC: 37776 AN: 152154 Hom.: 5804 Cov.: 32 AF XY: 0.259 AC XY: 19285 AN XY: 74394

Gnomad4 AFR AF: 0.0685

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.260

Alfa AF: 0.289 Hom.: 14756

Bravo AF: 0.239

Asia WGS AF: 0.397 AC: 1379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13252298; hg19: chr8-128095156; COSMIC: COSV73056794;