8-127281221-A-G

Variant names:

• chr8-127281221-A-G
• rs185852
• ENST00000644021.1:n.148+36437A>G

Variant summary

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

The ENST00000644021.1(PCAT1):​n.148+36437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,226 control chromosomes in the GnomAD database, including 50,797 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 0.81 (50797 hom., cov: 33)
• Consequence: PCAT1 ENST00000644021.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 6 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]

ENSG00000287781 (HGNC:):

CASC21 (HGNC:49836): (cancer susceptibility 21)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644021.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.148+36437A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCAT1	ENST00000644021.1		n.148+36437A>G		intron	N/A
	PCAT1	ENST00000645463.1		n.856-11591A>G		intron	N/A
	PCAT1	ENST00000646670.1		n.1065-58060A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123590 AN: 152108 Hom.: 50754 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.813 AC: 123688 AN: 152226 Hom.: 50797 Cov.: 33 AF XY: 0.803 AC XY: 59727 AN XY: 74412

African (AFR) AF: 0.917 AC: 38104 AN: 41552

American (AMR) AF: 0.792 AC: 12108 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2754 AN: 3466

East Asian (EAS) AF: 0.607 AC: 3148 AN: 5188

South Asian (SAS) AF: 0.615 AC: 2965 AN: 4820

European-Finnish (FIN) AF: 0.740 AC: 7831 AN: 10576

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54074 AN: 68008

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.799 Hom.: 23040

Bravo AF: 0.827

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs185852; hg19: chr8-128293466;