chr6-31169982-T-C

Variant names:

• chr6-31169982-T-C
• rs3132522
• NM_002701.6:c.405+234A>G

Variant summary

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

The NM_002701.6(POU5F1):​c.405+234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 650,386 control chromosomes in the GnomAD database, including 186,661 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 (46489 hom., cov: 31)
  • Exomes 𝑓: 0.75 (140172 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 11 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=-0.91).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.405+234A>G		intron	N/A	NP_002692.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.405+234A>G		intron	N/A	ENSP00000259915.7
	POU5F1	ENST00000441888.7	TSL:1	c.-183-3935A>G		intron	N/A	ENSP00000389359.2
	POU5F1	ENST00000461401.1	TSL:1	n.443+234A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118462 AN: 151816 Hom.: 46451 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.816

GnomAD4 exome AF: 0.747 AC: 372510 AN: 498452 Hom.: 140172 Cov.: 6 AF XY: 0.745 AC XY: 193674 AN XY: 259874

African (AFR) AF: 0.848 AC: 11356 AN: 13396

American (AMR) AF: 0.791 AC: 14780 AN: 18694

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 11898 AN: 13930

East Asian (EAS) AF: 0.637 AC: 19831 AN: 31132

South Asian (SAS) AF: 0.711 AC: 33014 AN: 46440

European-Finnish (FIN) AF: 0.743 AC: 21840 AN: 29402

Middle Eastern (MID) AF: 0.834 AC: 1734 AN: 2078

European-Non Finnish (NFE) AF: 0.750 AC: 236874 AN: 315722

Other (OTH) AF: 0.766 AC: 21183 AN: 27658

GnomAD4 genome AF: 0.780 AC: 118554 AN: 151934 Hom.: 46489 Cov.: 31 AF XY: 0.779 AC XY: 57837 AN XY: 74220

African (AFR) AF: 0.847 AC: 35107 AN: 41460

American (AMR) AF: 0.804 AC: 12291 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2990 AN: 3468

East Asian (EAS) AF: 0.679 AC: 3474 AN: 5118

South Asian (SAS) AF: 0.687 AC: 3312 AN: 4822

European-Finnish (FIN) AF: 0.749 AC: 7908 AN: 10560

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50764 AN: 67914

Other (OTH) AF: 0.815 AC: 1719 AN: 2110

Alfa AF: 0.750 Hom.: 27445

Bravo AF: 0.790

Asia WGS AF: 0.755 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.42
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3132522; hg19: chr6-31137759;