chr8-127265394-A-C

Variant names:

• chr8-127265394-A-C
• rs16902056
• ENST00000644021.1:n.148+20610A>C

Variant summary

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

The ENST00000644021.1(PCAT1):​n.148+20610A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,322 control chromosomes in the GnomAD database, including 374 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 0.064 (374 hom., cov: 32)
• Consequence: PCAT1 ENST00000644021.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.148+20610A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCAT1	ENST00000644021.1	n.148+20610A>C		intron_variant	Intron 1 of 3
PCAT1	ENST00000645463.1	n.856-27418A>C		intron_variant	Intron 6 of 6
PCAT1	ENST00000646670.1	n.1065-73887A>C		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9737 AN: 152204 Hom.: 369 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0640 AC: 9754 AN: 152322 Hom.: 374 Cov.: 32 AF XY: 0.0636 AC XY: 4736 AN XY: 74492

African (AFR) AF: 0.0496 AC: 2063 AN: 41568

American (AMR) AF: 0.0470 AC: 719 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5192

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4824

European-Finnish (FIN) AF: 0.0698 AC: 741 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0806 AC: 5486 AN: 68034

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0731 Hom.: 294

Bravo AF: 0.0607

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.41
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs16902056; hg19: chr8-128277639;