ENST00000441888.7:c.-183-5628A>G

Variant names:

• chr6-31171675-T-C
• rs879882
• ENST00000441888.7:c.-183-5628A>G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 148,632 control chromosomes in the GnomAD database, including 27,658 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 0.61 (27658 hom., cov: 24)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 57 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-183-5628A>G		intron	N/A	ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 90698 AN: 148518 Hom.: 27650 Cov.: 24

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.700

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.611 AC: 90745 AN: 148632 Hom.: 27658 Cov.: 24 AF XY: 0.609 AC XY: 44042 AN XY: 72344

African (AFR) AF: 0.545 AC: 21877 AN: 40114

American (AMR) AF: 0.662 AC: 9896 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2605 AN: 3464

East Asian (EAS) AF: 0.464 AC: 2250 AN: 4850

South Asian (SAS) AF: 0.560 AC: 2580 AN: 4606

European-Finnish (FIN) AF: 0.643 AC: 6427 AN: 9992

Middle Eastern (MID) AF: 0.688 AC: 198 AN: 288

European-Non Finnish (NFE) AF: 0.637 AC: 42936 AN: 67390

Other (OTH) AF: 0.618 AC: 1282 AN: 2076

Alfa AF: 0.625 Hom.: 84663

Bravo AF: 0.604

Asia WGS AF: 0.547 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		-0.26
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: rs879882; hg19: chr6-31139452;