8-127412547-A-G

Variant names:

• chr8-127412547-A-G
• rs7014346
• ENST00000501396.6:n.546+8282T>C

Variant summary

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

The ENST00000465342.4(POU5F1B):​c.-559-2341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,006 control chromosomes in the GnomAD database, including 31,072 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 0.64 (31072 hom., cov: 31)
• Consequence: POU5F1B ENST00000465342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 130 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465342.4. 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+8282T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+8282T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+8282T>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+8282T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96826 AN: 151886 Hom.: 31046 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.637 AC: 96903 AN: 152006 Hom.: 31072 Cov.: 31 AF XY: 0.642 AC XY: 47699 AN XY: 74306

African (AFR) AF: 0.602 AC: 24939 AN: 41436

American (AMR) AF: 0.690 AC: 10540 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3472

East Asian (EAS) AF: 0.712 AC: 3684 AN: 5172

South Asian (SAS) AF: 0.662 AC: 3191 AN: 4818

European-Finnish (FIN) AF: 0.664 AC: 7003 AN: 10550

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43246 AN: 67962

Other (OTH) AF: 0.660 AC: 1397 AN: 2116

Alfa AF: 0.640 Hom.: 146582

Bravo AF: 0.637

Asia WGS AF: 0.680 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		0.062

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7014346;

hg19: chr8-128424792;