6-31172296-G-A

Variant names:

• chr6-31172296-G-A
• rs3094190
• ENST00000441888.7:c.-183-6249C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441888.7(POU5F1):​c.-183-6249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,704 control chromosomes in the GnomAD database, including 29,589 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 0.62 (29589 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441888.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-183-6249C>T		intron	N/A	ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94573 AN: 151586 Hom.: 29563 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.624 AC: 94640 AN: 151704 Hom.: 29589 Cov.: 31 AF XY: 0.627 AC XY: 46471 AN XY: 74136

African (AFR) AF: 0.649 AC: 26804 AN: 41312

American (AMR) AF: 0.652 AC: 9952 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2252 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2957 AN: 5126

South Asian (SAS) AF: 0.666 AC: 3213 AN: 4822

European-Finnish (FIN) AF: 0.657 AC: 6901 AN: 10502

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40426 AN: 67894

Other (OTH) AF: 0.631 AC: 1332 AN: 2110

Alfa AF: 0.607 Hom.: 18264

Bravo AF: 0.624

Asia WGS AF: 0.617 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.41
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3094190; hg19: chr6-31140073;