rs28383834

Positions:

• chr6-31172185-G-GC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000441888.7(POU5F1):​c.-183-6139_-183-6138insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 151,980 control chromosomes in the GnomAD database, including 229 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.047 (229 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0873 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.-183-6139_-183-6138insG		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7140 AN: 151862 Hom.: 229 Cov.: 31

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0528

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

GnomAD4 genome AF: 0.0470 AC: 7139 AN: 151980 Hom.: 229 Cov.: 31 AF XY: 0.0447 AC XY: 3320 AN XY: 74306

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0523

Alfa AF: 0.0379 Hom.: 19

Bravo AF: 0.0552

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28383834; hg19: chr6-31139962;