rs9263816

Positions:

• chr6-31171020-G-T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-4973C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,140 control chromosomes in the GnomAD database, including 1,815 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 (1815 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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 (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-4973C>A		intron_variant		1		ENSP00000389359

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22637 AN: 152022 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.149 AC: 22684 AN: 152140 Hom.: 1815 Cov.: 32 AF XY: 0.147 AC XY: 10904 AN XY: 74376

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.0735

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.168

Alfa AF: 0.153 Hom.: 217

Bravo AF: 0.151

Asia WGS AF: 0.113 AC: 397 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	5.1
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9263816; hg19: chr6-31138797;