rs885951

Variant names:

• chr6-31172314-C-A
• rs885951
• ENST00000441888.7:c.-183-6267G>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6267G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,742 control chromosomes in the GnomAD database, including 13,614 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 0.42 (13614 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 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.-183-6267G>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64060 AN: 151624 Hom.: 13611 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.422 AC: 64085 AN: 151742 Hom.: 13614 Cov.: 31 AF XY: 0.417 AC XY: 30907 AN XY: 74154

African (AFR) AF: 0.446 AC: 18447 AN: 41344

American (AMR) AF: 0.435 AC: 6643 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1955 AN: 5130

South Asian (SAS) AF: 0.358 AC: 1723 AN: 4812

European-Finnish (FIN) AF: 0.360 AC: 3798 AN: 10538

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28885 AN: 67882

Other (OTH) AF: 0.400 AC: 842 AN: 2104

Alfa AF: 0.435 Hom.: 4314

Bravo AF: 0.429

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		-0.18
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: rs885951; hg19: chr6-31140091;