rs885950

Variant names:

• chr6-31172375-A-C
• rs885950
• ENST00000441888.7:c.-183-6328T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31172375-A-C
• chr6-31172375-A-T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,844 control chromosomes in the GnomAD database, including 13,726 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 (13726 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 33 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 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.-183-6328T>G		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64379 AN: 151726 Hom.: 13722 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.424 AC: 64408 AN: 151844 Hom.: 13726 Cov.: 31 AF XY: 0.420 AC XY: 31125 AN XY: 74188

African (AFR) AF: 0.439 AC: 18173 AN: 41394

American (AMR) AF: 0.443 AC: 6759 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1956 AN: 5142

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4816

European-Finnish (FIN) AF: 0.366 AC: 3850 AN: 10532

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29154 AN: 67908

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.432 Hom.: 35207

Bravo AF: 0.430

Asia WGS AF: 0.394 AC: 1371 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		0.66
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: rs885950; hg19: chr6-31140152;