rs17197220

chr6-31171354-T-C

Variant summary

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

The ENST00000441888.7(POU5F1):c.-183-5307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,194 control chromosomes in the GnomAD database, including 214 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 0.042 (214 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0772 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.-183-5307A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6438 AN: 152076 Hom.: 213 Cov.: 31

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0423 AC: 6435 AN: 152194 Hom.: 214 Cov.: 31 AF XY: 0.0435 AC XY: 3235 AN XY: 74398

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0586

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0493 Hom.: 30

Bravo AF: 0.0424

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.0
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17197220; hg19: chr6-31139131;