8-127395871-C-T

Variant names:

• chr8-127395871-C-T
• rs10505476
• ENST00000501396.6:n.546+24958G>A

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-19017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,028 control chromosomes in the GnomAD database, including 12,973 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 0.37 (12973 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 20 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645438.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1176+24958G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+24958G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+24958G>A		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+24958G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55626 AN: 151910 Hom.: 12938 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.366 AC: 55706 AN: 152028 Hom.: 12973 Cov.: 32 AF XY: 0.361 AC XY: 26849 AN XY: 74310

African (AFR) AF: 0.669 AC: 27726 AN: 41462

American (AMR) AF: 0.210 AC: 3215 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3464

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5164

South Asian (SAS) AF: 0.165 AC: 795 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3349 AN: 10562

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17350 AN: 67960

Other (OTH) AF: 0.327 AC: 692 AN: 2116

Alfa AF: 0.278 Hom.: 13768

Bravo AF: 0.374

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs10505476; hg19: chr8-128408116;