ENST00000441888.7:c.-183-6223C>T

Variant names:

• chr6-31172270-G-A
• rs1265159
• ENST00000441888.7:c.-183-6223C>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,064 control chromosomes in the GnomAD database, including 3,534 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 0.21 (3534 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 49 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.-183-6223C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32010 AN: 151946 Hom.: 3530 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.211 AC: 32022 AN: 152064 Hom.: 3534 Cov.: 32 AF XY: 0.201 AC XY: 14952 AN XY: 74356

African (AFR) AF: 0.248 AC: 10268 AN: 41446

American (AMR) AF: 0.150 AC: 2289 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3466

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5172

South Asian (SAS) AF: 0.113 AC: 545 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10592

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15562 AN: 67958

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.223 Hom.: 12270

Bravo AF: 0.214

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		1.2
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: rs1265159; hg19: chr6-31140047;