rs1265158

Variant names:

• chr6-31172964-C-G
• rs1265158
• ENST00000441888.7:c.-183-6917G>C

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6917G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,732 control chromosomes in the GnomAD database, including 11,535 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 0.38 (11535 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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.-183-6917G>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58066 AN: 151614 Hom.: 11526 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.383 AC: 58091 AN: 151732 Hom.: 11535 Cov.: 31 AF XY: 0.377 AC XY: 27949 AN XY: 74114

African (AFR) AF: 0.473 AC: 19568 AN: 41374

American (AMR) AF: 0.330 AC: 5021 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1894 AN: 3464

East Asian (EAS) AF: 0.254 AC: 1300 AN: 5116

South Asian (SAS) AF: 0.424 AC: 2034 AN: 4798

European-Finnish (FIN) AF: 0.285 AC: 2997 AN: 10526

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23952 AN: 67910

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.371 Hom.: 1555

Bravo AF: 0.390

Asia WGS AF: 0.397 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.63
PhyloP100		-0.90
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: rs1265158; hg19: chr6-31140741;