8-127091724-C-T

Variant names:

• chr8-127091724-C-T
• rs72725879
• ENST00000635449.1:n.11851C>T

Variant summary

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

The ENST00000635449.1(PRNCR1):​n.11851C>T 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 0.258 in 151,982 control chromosomes in the GnomAD database, including 5,905 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 0.26 (5905 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PRNCR1 ENST00000635449.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRNCR1	NR_109833.1	n.11851C>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRNCR1	ENST00000635449.1	n.11851C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
CASC19	ENST00000642100.1	n.418-12591G>A		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+85106C>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39204 AN: 151864 Hom.: 5892 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.240

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.258 AC: 39270 AN: 151982 Hom.: 5905 Cov.: 32 AF XY: 0.261 AC XY: 19367 AN XY: 74288

African (AFR) AF: 0.349 AC: 14442 AN: 41432

American (AMR) AF: 0.265 AC: 4043 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3522 AN: 5160

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2004 AN: 10540

Middle Eastern (MID) AF: 0.166 AC: 48 AN: 290

European-Non Finnish (NFE) AF: 0.188 AC: 12783 AN: 67972

Other (OTH) AF: 0.246 AC: 519 AN: 2114

Alfa AF: 0.222 Hom.: 506

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.51
PhyloP100		-0.97

Splicing

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

Other links and lift over

dbSNP: rs72725879; hg19: chr8-128103969; COSMIC: COSV73056813;