8-127330621-A-G

Variant names:

• chr8-127330621-A-G
• rs17464492
• ENST00000501396.6:n.547-7467T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000501396.6(CASC8):​n.547-7467T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,120 control chromosomes in the GnomAD database, including 4,979 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 0.25 (4979 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 19 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 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+8395A>G		intron	N/A
	CASC8	NR_117100.1		n.1177-40561T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.547-7467T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-40561T>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-40561T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37567 AN: 152002 Hom.: 4976 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.247 AC: 37595 AN: 152120 Hom.: 4979 Cov.: 32 AF XY: 0.244 AC XY: 18150 AN XY: 74378

African (AFR) AF: 0.208 AC: 8613 AN: 41478

American (AMR) AF: 0.203 AC: 3099 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3470

East Asian (EAS) AF: 0.0531 AC: 275 AN: 5180

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2440 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19535 AN: 67988

Other (OTH) AF: 0.264 AC: 556 AN: 2110

Alfa AF: 0.270 Hom.: 12746

Bravo AF: 0.239

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs17464492; hg19: chr8-128342866; COSMIC: COSV72371402;