ENST00000441888.7:c.-183-5216G>T

Variant names:

• chr6-31171263-C-A
• rs9263818
• ENST00000441888.7:c.-183-5216G>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5216G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,042 control chromosomes in the GnomAD database, including 1,703 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 0.14 (1703 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-5216G>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21985 AN: 151924 Hom.: 1695 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.145 AC: 22030 AN: 152042 Hom.: 1703 Cov.: 31 AF XY: 0.142 AC XY: 10527 AN XY: 74312

African (AFR) AF: 0.158 AC: 6551 AN: 41454

American (AMR) AF: 0.132 AC: 2014 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.0729 AC: 377 AN: 5172

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4822

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10756 AN: 67960

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.149 Hom.: 438

Bravo AF: 0.147

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		-2.5
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: rs9263818; hg19: chr6-31139040;