rs2269713

Positions:

• chr6-31173350-A-G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-184+7269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,164 control chromosomes in the GnomAD database, including 840 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 0.082 (840 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 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.-184+7269T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12466 AN: 152046 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0842

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

GnomAD4 genome AF: 0.0820 AC: 12483 AN: 152164 Hom.: 840 Cov.: 32 AF XY: 0.0837 AC XY: 6231 AN XY: 74408

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.0453

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0434 Hom.: 441

Bravo AF: 0.0873

Asia WGS AF: 0.153 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269713; hg19: chr6-31141127;