rs3094190

chr6-31172296-G-Achr6-31172296-G-C

Variant summary

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

The ENST00000441888.7(POU5F1):c.-183-6249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,704 control chromosomes in the GnomAD database, including 29,589 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 0.62 (29589 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-6249C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94573 AN: 151586 Hom.: 29563 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.624 AC: 94640 AN: 151704 Hom.: 29589 Cov.: 31 AF XY: 0.627 AC XY: 46471 AN XY: 74136

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.631

Alfa AF: 0.567 Hom.: 5604

Bravo AF: 0.624

Asia WGS AF: 0.617 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.1
Dann	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3094190; hg19: chr6-31140073;