Genetic Variant POU5F1:c.405+361C>G (chr6-31169855-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002701.6(POU5F1):c.405+361C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 381,174 control chromosomes in the GnomAD database, including 4,075 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 0.15 ( 1733 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2342 hom. )

Consequence

POU5F1
NM_002701.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.530

Publications

9 publications found

Variant links:

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]

POU5F1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6 link	c.405+361C>G		intron_variant	Intron 1 of 4	ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
POU5F1	ENST00000259915.13 link	c.405+361C>G	intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7	Q01860-1
POU5F1	ENST00000441888.7 link	c.-183-3808C>G	intron_variant	Intron 1 of 4	1		ENSP00000389359.2	F2Z381
POU5F1	ENST00000461401.1 link	n.443+361C>G	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22145

AN:

152062

Hom.:

1725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0923

Gnomad EAS

AF:

0.0729

Gnomad SAS

AF:

0.0667

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.131

AC:

29989

AN:

228994

Hom.:

2342

AF XY:

0.128

AC XY:

15070

AN XY:

117538

show subpopulations

African (AFR)

AF:

0.153

AC:

1197

AN:

7828

American (AMR)

AF:

0.114

AC:

1081

AN:

9492

Ashkenazi Jewish (ASJ)

AF:

0.0856

AC:

673

AN:

7858

East Asian (EAS)

AF:

0.0359

AC:

611

AN:

17016

South Asian (SAS)

AF:

0.0686

AC:

1236

AN:

18030

European-Finnish (FIN)

AF:

0.111

AC:

1469

AN:

13198

Middle Eastern (MID)

AF:

0.137

AC:

152

AN:

1110

European-Non Finnish (NFE)

AF:

0.155

AC:

21661

AN:

140138

Other (OTH)

AF:

0.133

AC:

1909

AN:

14324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1235

2471

3706

4942

6177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22190

AN:

152180

Hom.:

1733

Cov.:

AF XY:

0.143

AC XY:

10621

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.160

AC:

6632

AN:

41512

American (AMR)

AF:

0.133

AC:

2032

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0923

AC:

320

AN:

3468

East Asian (EAS)

AF:

0.0730

AC:

378

AN:

5176

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4824

European-Finnish (FIN)

AF:

0.115

AC:

1217

AN:

10600

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10791

AN:

67984

Other (OTH)

AF:

0.158

AC:

335

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

976

1952

2929

3905

4881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0626

Hom.:

Bravo

AF:

0.147

Asia WGS

AF:

0.101

AC:

352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.7

(source)

DANN

Benign

0.48

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over