chr8-127366717-G-T

Position:

• chr8-127366717-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645438.1(POU5F1B):​c.-560+27282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,762 control chromosomes in the GnomAD database, including 24,112 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 0.56 (24112 hom., cov: 31)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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

Verdict is Benign. Variant got -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 = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-25787G>T		intron_variant
CASC8	NR_117100.1	n.1176+54112C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-43563C>A		intron_variant		1
CASC8	ENST00000502082.5	n.1176+54112C>A		intron_variant		1
PCAT1	ENST00000521586.2	n.290-25787G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85241 AN: 151644 Hom.: 24101 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.562 AC: 85276 AN: 151762 Hom.: 24112 Cov.: 31 AF XY: 0.563 AC XY: 41737 AN XY: 74132

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.524

Alfa AF: 0.554 Hom.: 5885

Bravo AF: 0.548

Asia WGS AF: 0.510 AC: 1775 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11776330; hg19: chr8-128378963;