rs885950

chr6-31172375-A-Cchr6-31172375-A-T

Variant summary

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

The ENST00000441888.7(POU5F1):c.-183-6328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,844 control chromosomes in the GnomAD database, including 13,726 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 (13726 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 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.-183-6328T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64379 AN: 151726 Hom.: 13722 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.424 AC: 64408 AN: 151844 Hom.: 13726 Cov.: 31 AF XY: 0.420 AC XY: 31125 AN XY: 74188

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.406

Alfa AF: 0.426 Hom.: 4627

Bravo AF: 0.430

Asia WGS AF: 0.394 AC: 1371 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.1
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs885950; hg19: chr6-31140152;