rs16902149

Positions:

• chr8-127394860-G-C

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:):

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]

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/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+25969C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+25969C>G		intron_variant		1
CASC8	ENST00000502082.5	n.1176+25969C>G		intron_variant		1
CASC8	ENST00000523825.2	n.546+25969C>G		intron_variant		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;