8-127091810-G-T

Variant names:

• chr8-127091810-G-T
• rs7463708
• ENST00000635449.1:n.11937G>T

Variant summary

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

The ENST00000635449.1(PRNCR1):​n.11937G>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 0.271 in 149,672 control chromosomes in the GnomAD database, including 5,864 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 0.27 (5864 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PRNCR1 ENST00000635449.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 39 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRNCR1	NR_109833.1	n.11937G>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.11937G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
CASC19	ENST00000642100.1	n.418-12677C>A		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+85192G>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.271 AC: 40506 AN: 149564 Hom.: 5854 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.271 AC: 40550 AN: 149668 Hom.: 5864 Cov.: 32 AF XY: 0.272 AC XY: 19888 AN XY: 73186

African (AFR) AF: 0.237 AC: 9293 AN: 39250

American (AMR) AF: 0.292 AC: 4428 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3437 AN: 5152

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4816

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10570

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17710 AN: 67966

Other (OTH) AF: 0.280 AC: 584 AN: 2084

Alfa AF: 0.270 Hom.: 8287

Bravo AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.52
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs7463708; hg19: chr8-128104055;