rs16902124

Positions:

• chr8-127344972-G-A

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-560+5537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,228 control chromosomes in the GnomAD database, including 602 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 0.073 (602 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.457+5537G>A		intron_variant
CASC8	NR_117100.1	n.1177-54912C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-21818C>T		intron_variant		1
CASC8	ENST00000502082.5	n.1177-54912C>T		intron_variant		1
PCAT1	ENST00000521586.2	n.289+5537G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11157 AN: 152110 Hom.: 601 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0734 AC: 11173 AN: 152228 Hom.: 602 Cov.: 32 AF XY: 0.0722 AC XY: 5376 AN XY: 74426

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.0620 Hom.: 349

Bravo AF: 0.0883

Asia WGS AF: 0.109 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16902124; hg19: chr8-128357218;