6-31172755-A-G

Position:

• chr6-31172755-A-G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6708T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,812 control chromosomes in the GnomAD database, including 23,057 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 0.54 (23057 hom., cov: 30)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 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.-183-6708T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82635 AN: 151696 Hom.: 23047 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.545 AC: 82679 AN: 151812 Hom.: 23057 Cov.: 30 AF XY: 0.539 AC XY: 39976 AN XY: 74172

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.539

Alfa AF: 0.507 Hom.: 25845

Bravo AF: 0.560

Asia WGS AF: 0.531 AC: 1845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs885948; hg19: chr6-31140532;