8-127341494-A-G

Position:

• chr8-127341494-A-G

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-560+2059A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,002 control chromosomes in the GnomAD database, including 7,899 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 0.31 (7899 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.457+2059A>G		intron_variant
CASC8	NR_117100.1	n.1177-51434T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-18340T>C		intron_variant		1
CASC8	ENST00000502082.5	n.1177-51434T>C		intron_variant		1
PCAT1	ENST00000521586.2	n.289+2059A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47695 AN: 151884 Hom.: 7885 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.314 AC: 47763 AN: 152002 Hom.: 7899 Cov.: 32 AF XY: 0.309 AC XY: 22983 AN XY: 74298

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.357

Alfa AF: 0.316 Hom.: 1800

Bravo AF: 0.331

Asia WGS AF: 0.291 AC: 1009 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13262406; hg19: chr8-128353739;