8-127267029-G-A

Variant names:

• chr8-127267029-G-A
• rs10956354
• ENST00000644021.1:n.148+22245G>A

Variant summary

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

The NR_117099.1(CASC21):​n.148+22245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 152,018 control chromosomes in the GnomAD database, including 417 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 0.048 (417 hom., cov: 32)
• Consequence: CASC21 NR_117099.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_117099.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.148+22245G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCAT1	ENST00000644021.1		n.148+22245G>A		intron	N/A
	PCAT1	ENST00000645463.1		n.856-25783G>A		intron	N/A
	PCAT1	ENST00000646670.1		n.1065-72252G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7321 AN: 151926 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0483 AC: 7350 AN: 152018 Hom.: 417 Cov.: 32 AF XY: 0.0526 AC XY: 3903 AN XY: 74266

African (AFR) AF: 0.0299 AC: 1239 AN: 41482

American (AMR) AF: 0.104 AC: 1581 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5166

South Asian (SAS) AF: 0.0818 AC: 394 AN: 4816

European-Finnish (FIN) AF: 0.0598 AC: 629 AN: 10524

Middle Eastern (MID) AF: 0.0175 AC: 5 AN: 286

European-Non Finnish (NFE) AF: 0.0232 AC: 1576 AN: 68006

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.0367 Hom.: 180

Bravo AF: 0.0555

Asia WGS AF: 0.209 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.39
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs10956354; hg19: chr8-128279274;