8-127327181-G-A

Variant names:

• chr8-127327181-G-A
• rs424281
• ENST00000501396.6:n.547-4027C>T

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-4027C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,882 control chromosomes in the GnomAD database, including 24,800 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 0.57 (24800 hom., cov: 31)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 5 publications found

Genes affected

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

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]

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]

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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.302+4955G>A		intron	N/A
	CASC8	NR_117100.1		n.1177-37121C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.547-4027C>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-37121C>T		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-37121C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85871 AN: 151764 Hom.: 24763 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.566 AC: 85965 AN: 151882 Hom.: 24800 Cov.: 31 AF XY: 0.577 AC XY: 42794 AN XY: 74224

African (AFR) AF: 0.503 AC: 20846 AN: 41418

American (AMR) AF: 0.670 AC: 10237 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1826 AN: 3462

East Asian (EAS) AF: 0.817 AC: 4228 AN: 5172

South Asian (SAS) AF: 0.714 AC: 3434 AN: 4808

European-Finnish (FIN) AF: 0.596 AC: 6269 AN: 10526

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37058 AN: 67900

Other (OTH) AF: 0.585 AC: 1234 AN: 2108

Alfa AF: 0.555 Hom.: 65290

Bravo AF: 0.568

Asia WGS AF: 0.780 AC: 2709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.24
PhyloP100		-0.013

Splicing

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

Other links and lift over

dbSNP: rs424281; hg19: chr8-128339426;