8-127390708-C-T

Variant names:

• chr8-127390708-C-T
• rs10441525
• ENST00000501396.6:n.546+30121G>A

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-24180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,208 control chromosomes in the GnomAD database, including 59,080 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 0.88 (59080 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 4 publications found

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

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]

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]

CASC21 (HGNC:49836): (cancer susceptibility 21)

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 = 0.902 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
	CASC21	NR_117099.1		n.458-1796C>T		intron	N/A
	CASC8	NR_117100.1		n.1176+30121G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+30121G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+30121G>A		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-1796C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133891 AN: 152090 Hom.: 59039 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.880 AC: 133991 AN: 152208 Hom.: 59080 Cov.: 32 AF XY: 0.882 AC XY: 65580 AN XY: 74394

African (AFR) AF: 0.909 AC: 37767 AN: 41528

American (AMR) AF: 0.814 AC: 12447 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3223 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4491 AN: 5176

South Asian (SAS) AF: 0.848 AC: 4085 AN: 4820

European-Finnish (FIN) AF: 0.923 AC: 9774 AN: 10592

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.872 AC: 59325 AN: 68022

Other (OTH) AF: 0.862 AC: 1819 AN: 2110

Alfa AF: 0.861 Hom.: 15757

Bravo AF: 0.869

Asia WGS AF: 0.847 AC: 2945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.24
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs10441525; hg19: chr8-128402953;