6-31167929-C-T

Position:

• chr6-31167929-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.406-1882G>A		intron_variant		ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-1882G>A		intron_variant		1	NM_002701.6	ENSP00000259915	P1
POU5F1	ENST00000441888.7	c.-183-1882G>A		intron_variant		1		ENSP00000389359
POU5F1	ENST00000461401.1	n.444-1882G>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.807

Alfa AF: 0.766 Hom.: 16541

Bravo AF: 0.787

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs9263804; hg19: chr6-31135706;