rs3094191

Positions:

• chr6-31171133-T-C

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5086A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 151,594 control chromosomes in the GnomAD database, including 1,553 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 0.13 (1553 hom., cov: 30)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 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.-183-5086A>G		intron_variant		1		ENSP00000389359

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20226 AN: 151474 Hom.: 1550 Cov.: 30

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.133 AC: 20230 AN: 151594 Hom.: 1553 Cov.: 30 AF XY: 0.127 AC XY: 9422 AN XY: 74070

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.114

Alfa AF: 0.156 Hom.: 244

Bravo AF: 0.129

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3094191; hg19: chr6-31138910;