ENST00000441888.7:c.-183-6264A>G

Variant names:

• chr6-31172311-T-C
• rs3132519
• ENST00000441888.7:c.-183-6264A>G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6264A>G 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 151,644 control chromosomes in the GnomAD database, including 29,614 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 (29614 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• 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=-0.89).
• 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-183-6264A>G		intron	N/A	ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94583 AN: 151526 Hom.: 29584 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.624 AC: 94655 AN: 151644 Hom.: 29614 Cov.: 31 AF XY: 0.627 AC XY: 46482 AN XY: 74096

African (AFR) AF: 0.650 AC: 26830 AN: 41294

American (AMR) AF: 0.652 AC: 9954 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2954 AN: 5116

South Asian (SAS) AF: 0.666 AC: 3207 AN: 4812

European-Finnish (FIN) AF: 0.657 AC: 6894 AN: 10496

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

European-Non Finnish (NFE) AF: 0.596 AC: 40428 AN: 67884

Other (OTH) AF: 0.632 AC: 1330 AN: 2104

Alfa AF: 0.605 Hom.: 3602

Bravo AF: 0.625

Asia WGS AF: 0.618 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.46
PhyloP100		-0.37
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: rs3132519; hg19: chr6-31140088;