NM_002701.6:c.405+156T>A

Variant names:

• chr6-31170060-A-T
• rs3130504
• NM_002701.6:c.405+156T>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.405+156T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,209,756 control chromosomes in the GnomAD database, including 344,630 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 (46572 hom., cov: 32)
  • Exomes 𝑓: 0.75 (298058 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90
• Publications: 18 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 = 0.84 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.405+156T>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.405+156T>A		intron	N/A	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000441888.7	TSL:1	c.-183-4013T>A		intron	N/A	ENSP00000389359.2	F2Z381
	POU5F1	ENST00000461401.1	TSL:1	n.443+156T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118618 AN: 151940 Hom.: 46533 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.749 AC: 792336 AN: 1057698 Hom.: 298058 Cov.: 14 AF XY: 0.748 AC XY: 395521 AN XY: 528782

African (AFR) AF: 0.852 AC: 20668 AN: 24258

American (AMR) AF: 0.780 AC: 21371 AN: 27382

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 15797 AN: 18458

East Asian (EAS) AF: 0.641 AC: 22519 AN: 35106

South Asian (SAS) AF: 0.715 AC: 46503 AN: 65084

European-Finnish (FIN) AF: 0.742 AC: 28090 AN: 37860

Middle Eastern (MID) AF: 0.834 AC: 2680 AN: 3214

European-Non Finnish (NFE) AF: 0.749 AC: 599384 AN: 800170

Other (OTH) AF: 0.765 AC: 35324 AN: 46166

GnomAD4 genome AF: 0.781 AC: 118711 AN: 152058 Hom.: 46572 Cov.: 32 AF XY: 0.780 AC XY: 57919 AN XY: 74278

African (AFR) AF: 0.847 AC: 35176 AN: 41516

American (AMR) AF: 0.805 AC: 12304 AN: 15290

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

East Asian (EAS) AF: 0.679 AC: 3484 AN: 5128

South Asian (SAS) AF: 0.686 AC: 3311 AN: 4824

European-Finnish (FIN) AF: 0.749 AC: 7924 AN: 10574

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

European-Non Finnish (NFE) AF: 0.748 AC: 50806 AN: 67944

Other (OTH) AF: 0.817 AC: 1725 AN: 2112

Alfa AF: 0.761 Hom.: 5497

Bravo AF: 0.790

Asia WGS AF: 0.756 AC: 2630 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	0.16
DANN	Benign	0.57
PhyloP100		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs3130504; hg19: chr6-31137837;