8-127395198-A-G

Variant names:

• chr8-127395198-A-G
• rs10505477
• ENST00000501396.6:n.546+25631T>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+25631T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,070 control chromosomes in the GnomAD database, including 14,605 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 0.41 (14605 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 183 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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
	CASC8	NR_117100.1		n.1176+25631T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+25631T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+25631T>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+25631T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62273 AN: 151950 Hom.: 14603 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.410 AC: 62274 AN: 152070 Hom.: 14605 Cov.: 32 AF XY: 0.415 AC XY: 30858 AN XY: 74320

African (AFR) AF: 0.172 AC: 7119 AN: 41506

American (AMR) AF: 0.461 AC: 7046 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1736 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3113 AN: 5174

South Asian (SAS) AF: 0.516 AC: 2479 AN: 4808

European-Finnish (FIN) AF: 0.501 AC: 5284 AN: 10544

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34093 AN: 67978

Other (OTH) AF: 0.443 AC: 935 AN: 2110

Alfa AF: 0.475 Hom.: 85200

Bravo AF: 0.393

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.85
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs10505477; hg19: chr8-128407443;