8-127328663-C-T

Variant names:

• chr8-127328663-C-T
• rs16902104
• ENST00000501396.6:n.547-5509G>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-5509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,204 control chromosomes in the GnomAD database, including 1,662 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 0.14 (1662 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 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+6437C>T		intron	N/A
	CASC8	NR_117100.1		n.1177-38603G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.547-5509G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-38603G>A		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-38603G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20900 AN: 152086 Hom.: 1661 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.137 AC: 20916 AN: 152204 Hom.: 1662 Cov.: 32 AF XY: 0.145 AC XY: 10813 AN XY: 74402

African (AFR) AF: 0.0759 AC: 3152 AN: 41544

American (AMR) AF: 0.153 AC: 2342 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1333 AN: 5182

South Asian (SAS) AF: 0.171 AC: 826 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2551 AN: 10568

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 290

European-Non Finnish (NFE) AF: 0.147 AC: 9977 AN: 68000

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.135 Hom.: 4205

Bravo AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs16902104; hg19: chr8-128340908;