rs7013278

Positions:

• chr8-127402647-T-C
• chr8-127402647-T-G

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-559-12241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,008 control chromosomes in the GnomAD database, including 27,466 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 0.59 (27466 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+18182A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+18182A>G		intron_variant		1
CASC8	ENST00000502082.5	n.1176+18182A>G		intron_variant		1
CASC8	ENST00000523825.2	n.546+18182A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90129 AN: 151890 Hom.: 27451 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.593 AC: 90175 AN: 152008 Hom.: 27466 Cov.: 32 AF XY: 0.599 AC XY: 44511 AN XY: 74310

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.625

Alfa AF: 0.622 Hom.: 9384

Bravo AF: 0.588

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.75
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7013278; hg19: chr8-128414892;