chr8-127375606-T-C

Position:

• chr8-127375606-T-C

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-560+36171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,046 control chromosomes in the GnomAD database, including 12,704 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 0.40 (12704 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-16898T>C		intron_variant
CASC8	NR_117100.1	n.1176+45223A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+45223A>G		intron_variant		1
CASC8	ENST00000502082.5	n.1176+45223A>G		intron_variant		1
PCAT1	ENST00000521586.2	n.290-16898T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61293 AN: 151928 Hom.: 12702 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.403 AC: 61310 AN: 152046 Hom.: 12704 Cov.: 32 AF XY: 0.395 AC XY: 29335 AN XY: 74306

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.373

Alfa AF: 0.401 Hom.: 28573

Bravo AF: 0.399

Asia WGS AF: 0.209 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1562430; hg19: chr8-128387852;