NM_002701.6:c.405+219C>A

Variant names:

• chr6-31169997-G-T
• rs3094193
• NM_002701.6:c.405+219C>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+219C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 700,508 control chromosomes in the GnomAD database, including 130,552 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 0.63 (30426 hom., cov: 31)
  • Exomes 𝑓: 0.60 (100126 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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+219C>A		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+219C>A		intron	N/A	ENSP00000259915.7
	POU5F1	ENST00000441888.7	TSL:1	c.-183-3950C>A		intron	N/A	ENSP00000389359.2
	POU5F1	ENST00000461401.1	TSL:1	n.443+219C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95756 AN: 151704 Hom.: 30418 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.600 AC: 329234 AN: 548688 Hom.: 100126 Cov.: 7 AF XY: 0.600 AC XY: 171075 AN XY: 285104

African (AFR) AF: 0.689 AC: 9826 AN: 14252

American (AMR) AF: 0.667 AC: 13158 AN: 19734

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 10872 AN: 14312

East Asian (EAS) AF: 0.601 AC: 18958 AN: 31566

South Asian (SAS) AF: 0.603 AC: 29393 AN: 48720

European-Finnish (FIN) AF: 0.626 AC: 18676 AN: 29852

Middle Eastern (MID) AF: 0.655 AC: 1445 AN: 2206

European-Non Finnish (NFE) AF: 0.582 AC: 208751 AN: 358756

Other (OTH) AF: 0.620 AC: 18155 AN: 29290

GnomAD4 genome AF: 0.631 AC: 95802 AN: 151820 Hom.: 30426 Cov.: 31 AF XY: 0.632 AC XY: 46901 AN XY: 74162

African (AFR) AF: 0.687 AC: 28437 AN: 41406

American (AMR) AF: 0.663 AC: 10130 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2659 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3091 AN: 5108

South Asian (SAS) AF: 0.594 AC: 2862 AN: 4816

European-Finnish (FIN) AF: 0.633 AC: 6679 AN: 10546

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39757 AN: 67890

Other (OTH) AF: 0.648 AC: 1364 AN: 2106

Alfa AF: 0.613 Hom.: 50160

Bravo AF: 0.640

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.83
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs3094193; hg19: chr6-31137774;