rs753228

Variant names:

• chr8-126978010-C-T
• rs753228
• ENST00000519319.2:n.263-28545C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000519319.2(PCAT1):​n.263-28545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,282 control chromosomes in the GnomAD database, including 67 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 0.029 (67 hom., cov: 33)
• Consequence: PCAT1 ENST00000519319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 4 publications found

Genes affected

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]

LOC105375751 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0286 (4358/152282) while in subpopulation AFR AF = 0.043 (1787/41550). AF 95% confidence interval is 0.0413. There are 67 homozygotes in GnomAd4. There are 2148 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 67 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375751	NR_188069.1	n.664-28545C>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCAT1	ENST00000519319.2	n.263-28545C>T		intron_variant	Intron 3 of 4	2
PCAT1	ENST00000643079.1	n.10-28545C>T		intron_variant	Intron 1 of 3
PCAT1	ENST00000643101.1	n.162-28545C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4351 AN: 152164 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0286 AC: 4358 AN: 152282 Hom.: 67 Cov.: 33 AF XY: 0.0288 AC XY: 2148 AN XY: 74460

African (AFR) AF: 0.0430 AC: 1787 AN: 41550

American (AMR) AF: 0.0189 AC: 289 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4828

European-Finnish (FIN) AF: 0.0340 AC: 361 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1684 AN: 68014

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0257 Hom.: 40

Bravo AF: 0.0280

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs753228; hg19: chr8-127990255;