8-127366717-G-T

Variant names:

• chr8-127366717-G-T
• rs11776330
• ENST00000501396.6:n.547-43563C>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-43563C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,762 control chromosomes in the GnomAD database, including 24,112 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 0.56 (24112 hom., cov: 31)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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.458-25787G>T		intron	N/A
	CASC8	NR_117100.1		n.1176+54112C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.547-43563C>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+54112C>A		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-25787G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85241 AN: 151644 Hom.: 24101 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.562 AC: 85276 AN: 151762 Hom.: 24112 Cov.: 31 AF XY: 0.563 AC XY: 41737 AN XY: 74132

African (AFR) AF: 0.597 AC: 24712 AN: 41382

American (AMR) AF: 0.461 AC: 7031 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2006 AN: 3464

East Asian (EAS) AF: 0.526 AC: 2709 AN: 5152

South Asian (SAS) AF: 0.509 AC: 2441 AN: 4792

European-Finnish (FIN) AF: 0.651 AC: 6828 AN: 10486

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37923 AN: 67924

Other (OTH) AF: 0.524 AC: 1105 AN: 2108

Alfa AF: 0.555 Hom.: 11217

Bravo AF: 0.548

Asia WGS AF: 0.510 AC: 1775 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.49
PhyloP100		-0.66

Splicing

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

Other links and lift over

dbSNP: rs11776330; hg19: chr8-128378963;