6-31167929-C-T

Variant names:

• chr6-31167929-C-T
• rs9263804
• NM_002701.6:c.406-1882G>A

Variant summary

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

The NM_002701.6(POU5F1):​c.406-1882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,898 control chromosomes in the GnomAD database, including 46,115 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 0.78 (46115 hom., cov: 28)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 17 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002701.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.406-1882G>A		intron	N/A	NP_002692.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.406-1882G>A		intron	N/A	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000441888.7	TSL:1	c.-183-1882G>A		intron	N/A	ENSP00000389359.2	F2Z381
	POU5F1	ENST00000461401.1	TSL:1	n.444-1882G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117957 AN: 151780 Hom.: 46078 Cov.: 28

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.777 AC: 118048 AN: 151898 Hom.: 46115 Cov.: 28 AF XY: 0.775 AC XY: 57577 AN XY: 74260

African (AFR) AF: 0.847 AC: 35080 AN: 41426

American (AMR) AF: 0.796 AC: 12164 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3475 AN: 5136

South Asian (SAS) AF: 0.663 AC: 3185 AN: 4806

European-Finnish (FIN) AF: 0.749 AC: 7894 AN: 10538

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50579 AN: 67928

Other (OTH) AF: 0.807 AC: 1705 AN: 2112

Alfa AF: 0.774 Hom.: 33082

Bravo AF: 0.787

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.75
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9263804; hg19: chr6-31135706;