rs896324

Variant names:

• chr8-127384267-G-A
• rs896324
• ENST00000501396.6:n.546+36562C>T

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-30621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,136 control chromosomes in the GnomAD database, including 58,422 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 0.87 (58422 hom., cov: 30)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.903 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.458-8237G>A		intron	N/A
	CASC8	NR_117100.1		n.1176+36562C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+36562C>T		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+36562C>T		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-8237G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132914 AN: 152018 Hom.: 58385 Cov.: 30

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.874 AC: 133008 AN: 152136 Hom.: 58422 Cov.: 30 AF XY: 0.876 AC XY: 65145 AN XY: 74386

African (AFR) AF: 0.804 AC: 33328 AN: 41462

American (AMR) AF: 0.845 AC: 12911 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3323 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4430 AN: 5160

South Asian (SAS) AF: 0.849 AC: 4101 AN: 4828

European-Finnish (FIN) AF: 0.953 AC: 10111 AN: 10608

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61814 AN: 68010

Other (OTH) AF: 0.885 AC: 1872 AN: 2116

Alfa AF: 0.898 Hom.: 77298

Bravo AF: 0.859

Asia WGS AF: 0.851 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		0.0030

Splicing

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

Other links and lift over

dbSNP: rs896324; hg19: chr8-128396512;