8-127394754-G-A

Variant names:

• chr8-127394754-G-A
• rs16902148
• ENST00000501396.6:n.546+26075C>T

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-20134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,218 control chromosomes in the GnomAD database, including 152 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 0.044 (152 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0554 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+26075C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+26075C>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+26075C>T		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+26075C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6639 AN: 152098 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.0364

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0437 AC: 6647 AN: 152218 Hom.: 152 Cov.: 32 AF XY: 0.0456 AC XY: 3393 AN XY: 74424

African (AFR) AF: 0.0375 AC: 1557 AN: 41546

American (AMR) AF: 0.0194 AC: 297 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.0609 AC: 316 AN: 5186

South Asian (SAS) AF: 0.0469 AC: 226 AN: 4814

European-Finnish (FIN) AF: 0.0893 AC: 945 AN: 10588

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0440 AC: 2990 AN: 68004

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0406 Hom.: 27

Bravo AF: 0.0379

Asia WGS AF: 0.0450 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.60
DANN	Benign	0.74
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16902148; hg19: chr8-128406999;