8-127091692-T-C

Variant names:

• chr8-127091692-T-C
• rs1456315
• ENST00000635449.1:n.11819T>C

Variant summary

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

The ENST00000635449.1(PRNCR1):​n.11819T>C 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 0.588 in 152,004 control chromosomes in the GnomAD database, including 27,246 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 0.59 (27246 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PRNCR1 ENST00000635449.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 84 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRNCR1	NR_109833.1	n.11819T>C		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.11819T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
CASC19	ENST00000642100.1	n.418-12559A>G		intron_variant	Intron 1 of 1
PCAT1	ENST00000645463.1	n.855+85074T>C		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89316 AN: 151886 Hom.: 27244 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.606

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: 0.588 AC: 89339 AN: 152004 Hom.: 27246 Cov.: 32 AF XY: 0.585 AC XY: 43472 AN XY: 74304

African (AFR) AF: 0.460 AC: 19060 AN: 41438

American (AMR) AF: 0.548 AC: 8363 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1532 AN: 5172

South Asian (SAS) AF: 0.675 AC: 3252 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6876 AN: 10558

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45857 AN: 67970

Other (OTH) AF: 0.602 AC: 1274 AN: 2116

Alfa AF: 0.644 Hom.: 144661

Bravo AF: 0.570

Asia WGS AF: 0.461 AC: 1602 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	3.1
DANN	Benign	0.81
PhyloP100		0.51

Splicing

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

Other links and lift over

dbSNP: rs1456315; hg19: chr8-128103937;