ENST00000501396.6:n.546+15570A>G

Variant names:

• chr8-127405259-T-C
• rs10505474
• ENST00000501396.6:n.546+15570A>G

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+15570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,966 control chromosomes in the GnomAD database, including 20,355 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 0.48 (20355 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+15570A>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+15570A>G		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+15570A>G		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+15570A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73148 AN: 151848 Hom.: 20349 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.481 AC: 73167 AN: 151966 Hom.: 20355 Cov.: 32 AF XY: 0.488 AC XY: 36224 AN XY: 74272

African (AFR) AF: 0.183 AC: 7584 AN: 41454

American (AMR) AF: 0.627 AC: 9577 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3319 AN: 5158

South Asian (SAS) AF: 0.605 AC: 2910 AN: 4810

European-Finnish (FIN) AF: 0.571 AC: 6014 AN: 10534

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 39997 AN: 67942

Other (OTH) AF: 0.543 AC: 1148 AN: 2114

Alfa AF: 0.553 Hom.: 12853

Bravo AF: 0.472

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		0.026

Splicing

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

Other links and lift over

dbSNP: rs10505474; hg19: chr8-128417504;