rs4871789

Positions:

• chr8-127415816-A-G
• chr8-127415816-A-T

Variant summary

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

The NM_001395745.1(POU5F1B):​c.-51A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,465,806 control chromosomes in the GnomAD database, including 187,860 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 0.45 (16732 hom., cov: 33)
  • Exomes 𝑓: 0.51 (171128 hom.)
• Consequence: POU5F1B NM_001395745.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1B	NM_001395745.1	c.-51A>G		5_prime_UTR_variant	2/2		NP_001382674.1
CASC8	NR_117100.1	n.1176+5013T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+5013T>C		intron_variant		1
CASC8	ENST00000502082.5	n.1176+5013T>C		intron_variant		1
CASC8	ENST00000523825.2	n.546+5013T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68339 AN: 151990 Hom.: 16727 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.507 AC: 665702 AN: 1313698 Hom.: 171128 Cov.: 48 AF XY: 0.509 AC XY: 325335 AN XY: 639210

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.449 AC: 68360 AN: 152108 Hom.: 16732 Cov.: 33 AF XY: 0.456 AC XY: 33934 AN XY: 74346

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.481

Alfa AF: 0.499 Hom.: 32781

Bravo AF: 0.446

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.79

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: rs4871789; hg19: chr8-128428061; COSMIC: COSV66966705; COSMIC: COSV66966705;