rs7837328

Positions:

• chr8-127410882-A-G

Variant summary

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

The ENST00000465342.4(POU5F1B):​c.-560+1851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 145,450 control chromosomes in the GnomAD database, including 21,323 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 0.52 (21323 hom., cov: 23)
• Consequence: POU5F1B ENST00000465342.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+9947T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+9947T>C		intron_variant		1
CASC8	ENST00000502082.5	n.1176+9947T>C		intron_variant		1
CASC8	ENST00000523825.2	n.546+9947T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 76287 AN: 145366 Hom.: 21324 Cov.: 23

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.524 AC: 76287 AN: 145450 Hom.: 21323 Cov.: 23 AF XY: 0.527 AC XY: 36948 AN XY: 70150

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.571

Alfa AF: 0.585 Hom.: 49432

Bravo AF: 0.529

Asia WGS AF: 0.606 AC: 2104 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7837328; hg19: chr8-128423127;