8-127415475-C-T

Variant names:

• chr8-127415475-C-T
• rs4871022
• ENST00000501396.6:n.546+5354G>A

Variant summary

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

The NM_001395745.1(POU5F1B):​c.-392C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 181,604 control chromosomes in the GnomAD database, including 26,394 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 0.51 (21314 hom., cov: 32)
  • Exomes 𝑓: 0.57 (5080 hom.)
• Consequence: POU5F1B NM_001395745.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395745.1. 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
	POU5F1B	NM_001395745.1		c.-392C>T		5_prime_UTR	Exon 2 of 2	NP_001382674.1	Q06416
	CASC8	NR_117100.1		n.1176+5354G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+5354G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+5354G>A		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+5354G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76903 AN: 151834 Hom.: 21311 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.569 AC: 16866 AN: 29654 Hom.: 5080 Cov.: 2 AF XY: 0.573 AC XY: 8511 AN XY: 14856

African (AFR) AF: 0.238 AC: 268 AN: 1128

American (AMR) AF: 0.590 AC: 827 AN: 1402

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 706 AN: 1232

East Asian (EAS) AF: 0.666 AC: 1490 AN: 2236

South Asian (SAS) AF: 0.554 AC: 360 AN: 650

European-Finnish (FIN) AF: 0.563 AC: 582 AN: 1034

Middle Eastern (MID) AF: 0.604 AC: 93 AN: 154

European-Non Finnish (NFE) AF: 0.576 AC: 11447 AN: 19870

Other (OTH) AF: 0.561 AC: 1093 AN: 1948

GnomAD4 genome AF: 0.506 AC: 76920 AN: 151950 Hom.: 21314 Cov.: 32 AF XY: 0.512 AC XY: 37996 AN XY: 74248

African (AFR) AF: 0.265 AC: 10993 AN: 41454

American (AMR) AF: 0.638 AC: 9744 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2025 AN: 3464

East Asian (EAS) AF: 0.644 AC: 3318 AN: 5154

South Asian (SAS) AF: 0.594 AC: 2840 AN: 4782

European-Finnish (FIN) AF: 0.573 AC: 6047 AN: 10554

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40171 AN: 67952

Other (OTH) AF: 0.557 AC: 1175 AN: 2108

Alfa AF: 0.557 Hom.: 11521

Bravo AF: 0.501

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.55
PhyloP100		0.27
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4871022; hg19: chr8-128427720;