chr8-127417476-T-C

Position:

• chr8-127417476-T-C

Variant summary

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

The ENST00000465342.4(POU5F1B):​c.*530T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 155,558 control chromosomes in the GnomAD database, including 31,557 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 0.63 (30791 hom., cov: 31)
  • Exomes 𝑓: 0.62 (766 hom.)
• Consequence: POU5F1B ENST00000465342.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+3353A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+3353A>G		intron_variant		1
CASC8	ENST00000502082.5	n.1176+3353A>G		intron_variant		1
CASC8	ENST00000523825.2	n.546+3353A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95895 AN: 151572 Hom.: 30779 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.619 AC: 2394 AN: 3868 Hom.: 766 Cov.: 0 AF XY: 0.640 AC XY: 1138 AN XY: 1778

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.648

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.632 AC: 95942 AN: 151690 Hom.: 30791 Cov.: 31 AF XY: 0.640 AC XY: 47410 AN XY: 74124

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.655

Alfa AF: 0.651 Hom.: 54363

Bravo AF: 0.629

Asia WGS AF: 0.716 AC: 2487 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6985419; hg19: chr8-128429721;