rs885952

Positions:

• chr6-31171713-C-T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,434 control chromosomes in the GnomAD database, including 13,404 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 0.42 (13404 hom., cov: 28)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-5666G>A		intron_variant		1		ENSP00000389359

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63545 AN: 151316 Hom.: 13401 Cov.: 28

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.420 AC: 63569 AN: 151434 Hom.: 13404 Cov.: 28 AF XY: 0.414 AC XY: 30625 AN XY: 73968

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.390

Alfa AF: 0.418 Hom.: 9260

Bravo AF: 0.426

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs885952; hg19: chr6-31139490;