8-127375606-T-C

Variant names:

• chr8-127375606-T-C
• rs1562430
• ENST00000501396.6:n.546+45223A>G

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+45223A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,046 control chromosomes in the GnomAD database, including 12,704 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 0.40 (12704 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 90 publications found

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

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]

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. 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.458-16898T>C		intron	N/A
	CASC8	NR_117100.1		n.1176+45223A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+45223A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+45223A>G		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-16898T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61293 AN: 151928 Hom.: 12702 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.403 AC: 61310 AN: 152046 Hom.: 12704 Cov.: 32 AF XY: 0.395 AC XY: 29335 AN XY: 74306

African (AFR) AF: 0.460 AC: 19043 AN: 41430

American (AMR) AF: 0.297 AC: 4549 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.177 AC: 920 AN: 5184

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4812

European-Finnish (FIN) AF: 0.413 AC: 4362 AN: 10556

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28436 AN: 67982

Other (OTH) AF: 0.373 AC: 788 AN: 2114

Alfa AF: 0.405 Hom.: 57101

Bravo AF: 0.399

Asia WGS AF: 0.209 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.58
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs1562430; hg19: chr8-128387852;