rs16902149

Variant names:

• chr8-127394860-G-C
• rs16902149
• ENST00000501396.5:n.546+25969C>G

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-20028G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 152,150 control chromosomes in the GnomAD database, including 757 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 0.084 (756 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+25969C>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+25969C>G		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+25969C>G		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.2	n.546+25969C>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12713 AN: 152010 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0752

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 1 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0837 AC: 12737 AN: 152128 Hom.: 756 Cov.: 32 AF XY: 0.0791 AC XY: 5886 AN XY: 74372

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0791

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.0632

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0787 Hom.: 87

Bravo AF: 0.0892

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16902149; hg19: chr8-128407105;