rs17467139

Variant names:

• chr8-127399765-A-G
• rs17467139
• ENST00000501396.5:n.546+21064T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645438.1(POU5F1B):​c.-559-15123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 152,340 control chromosomes in the GnomAD database, including 148 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 0.037 (148 hom., cov: 33)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+21064T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+21064T>C		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+21064T>C		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.2	n.546+21064T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5575 AN: 152222 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0366 AC: 5576 AN: 152340 Hom.: 148 Cov.: 33 AF XY: 0.0344 AC XY: 2564 AN XY: 74498

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0545 Hom.: 155

Bravo AF: 0.0359

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17467139; hg19: chr8-128412010;