chr8-127391269-T-G

Position:

• chr8-127391269-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000645438.1(POU5F1B):​c.-559-23619T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,206 control chromosomes in the GnomAD database, including 563 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 0.079 (563 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-1235T>G		intron_variant
CASC8	NR_117100.1	n.1176+29560A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+29560A>C		intron_variant		1
CASC8	ENST00000502082.5	n.1176+29560A>C		intron_variant		1
PCAT1	ENST00000521586.2	n.290-1235T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12041 AN: 152088 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0792 AC: 12060 AN: 152206 Hom.: 563 Cov.: 32 AF XY: 0.0802 AC XY: 5970 AN XY: 74406

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0831

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0613 Hom.: 472

Bravo AF: 0.0753

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7844673; hg19: chr8-128403514;