rs1562871

Variant names:

• chr8-127389527-C-T
• rs1562871
• ENST00000501396.6:n.546+31302G>A

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-25361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,184 control chromosomes in the GnomAD database, including 48,686 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 0.80 (48686 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 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.458-2977C>T		intron	N/A
	CASC8	NR_117100.1		n.1176+31302G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+31302G>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+31302G>A		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-2977C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121473 AN: 152066 Hom.: 48660 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.799 AC: 121550 AN: 152184 Hom.: 48686 Cov.: 32 AF XY: 0.796 AC XY: 59230 AN XY: 74408

African (AFR) AF: 0.812 AC: 33711 AN: 41520

American (AMR) AF: 0.776 AC: 11880 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3076 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3349 AN: 5164

South Asian (SAS) AF: 0.656 AC: 3162 AN: 4820

European-Finnish (FIN) AF: 0.837 AC: 8862 AN: 10588

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54832 AN: 68006

Other (OTH) AF: 0.801 AC: 1690 AN: 2110

Alfa AF: 0.799 Hom.: 217567

Bravo AF: 0.795

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.15
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs1562871; hg19: chr8-128401772;