6-31173432-A-G

Variant names:

• chr6-31173432-A-G
• rs2269712
• ENST00000441888.7:c.-184+7187T>C

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-184+7187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,242 control chromosomes in the GnomAD database, including 47,166 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 0.79 (47166 hom., cov: 34)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 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.-184+7187T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119403 AN: 152124 Hom.: 47109 Cov.: 34

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.785 AC: 119514 AN: 152242 Hom.: 47166 Cov.: 34 AF XY: 0.783 AC XY: 58281 AN XY: 74438

African (AFR) AF: 0.871 AC: 36217 AN: 41568

American (AMR) AF: 0.784 AC: 11993 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2525 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3727 AN: 5170

South Asian (SAS) AF: 0.701 AC: 3379 AN: 4822

European-Finnish (FIN) AF: 0.764 AC: 8091 AN: 10596

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50894 AN: 67988

Other (OTH) AF: 0.809 AC: 1710 AN: 2114

Alfa AF: 0.766 Hom.: 33667

Bravo AF: 0.791

Asia WGS AF: 0.747 AC: 2600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.83
PhyloP100		-0.20
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: rs2269712; hg19: chr6-31141209;