ENST00000441888.7:c.-183-6708T>C

Variant names:

• chr6-31172755-A-G
• rs885948
• ENST00000441888.7:c.-183-6708T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 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.-183-6708T>C		intron	N/A	ENSP00000389359.2

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

African (AFR) AF: 0.662 AC: 27412 AN: 41406

American (AMR) AF: 0.547 AC: 8347 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2500 AN: 5132

South Asian (SAS) AF: 0.476 AC: 2285 AN: 4796

European-Finnish (FIN) AF: 0.417 AC: 4390 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33853 AN: 67894

Other (OTH) AF: 0.539 AC: 1139 AN: 2112

Alfa AF: 0.517 Hom.: 71269

Bravo AF: 0.560

Asia WGS AF: 0.531 AC: 1845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.40
PhyloP100		-0.41
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: rs885948; hg19: chr6-31140532;