rs9263817

Positions:

• chr6-31171140-G-A
• chr6-31171140-G-C

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,776 control chromosomes in the GnomAD database, including 1,882 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 0.15 (1882 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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.-183-5093C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22949 AN: 151660 Hom.: 1874 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0924

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.151 AC: 22993 AN: 151776 Hom.: 1882 Cov.: 31 AF XY: 0.148 AC XY: 10965 AN XY: 74130

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0924

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.165

Alfa AF: 0.147 Hom.: 206

Bravo AF: 0.154

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9263817; hg19: chr6-31138917;