chr8-127400902-C-T

Position:

• chr8-127400902-C-T

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-13986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,086 control chromosomes in the GnomAD database, including 21,523 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 0.51 (21517 hom., cov: 32)
  • Exomes 𝑓: 0.52 (6 hom.)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAT2	NR_109834.1	n.504C>T		non_coding_transcript_exon_variant	1/1
CASC8	NR_117100.1	n.1176+19927G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+19927G>A		intron_variant		1
CASC8	ENST00000502082.5	n.1176+19927G>A		intron_variant		1
CASC8	ENST00000523825.2	n.546+19927G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77806 AN: 151920 Hom.: 21511 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.522 AC: 24 AN: 46 Hom.: 6 Cov.: 0 AF XY: 0.528 AC XY: 19 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.553

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.512 AC: 77833 AN: 152040 Hom.: 21517 Cov.: 32 AF XY: 0.517 AC XY: 38449 AN XY: 74322

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.564

Alfa AF: 0.578 Hom.: 35724

Bravo AF: 0.508

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10808556; hg19: chr8-128413147;