Genetic Variant POU5F1:c.405+248G>A (chr6-31169968-C-T) – 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+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 621,108 control chromosomes in the GnomAD database, including 6,722 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 ( 1734 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4988 hom. )

Consequence

POU5F1
NM_002701.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

2 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:

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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=-0.82).

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+248G>A		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+248G>A	intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7	Q01860-1
POU5F1	ENST00000441888.7 link	c.-183-3921G>A	intron_variant	Intron 1 of 4	1		ENSP00000389359.2	F2Z381
POU5F1	ENST00000461401.1 link	n.443+248G>A	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22130

AN:

152012

Hom.:

1726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.0725

Gnomad SAS

AF:

0.0668

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.137

AC:

64062

AN:

468978

Hom.:

4988

Cov.:

AF XY:

0.134

AC XY:

32738

AN XY:

245054

show subpopulations

African (AFR)

AF:

0.155

AC:

1992

AN:

12836

American (AMR)

AF:

0.115

AC:

2105

AN:

18372

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

1229

AN:

13636

East Asian (EAS)

AF:

0.0357

AC:

1095

AN:

30704

South Asian (SAS)

AF:

0.0757

AC:

3422

AN:

45184

European-Finnish (FIN)

AF:

0.118

AC:

3401

AN:

28928

Middle Eastern (MID)

AF:

0.150

AC:

302

AN:

2018

European-Non Finnish (NFE)

AF:

0.161

AC:

46847

AN:

290798

Other (OTH)

AF:

0.138

AC:

3669

AN:

26502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2675

5351

8026

10702

13377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<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:

22175

AN:

152130

Hom.:

1734

Cov.:

AF XY:

0.143

AC XY:

10606

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.160

AC:

6632

AN:

41486

American (AMR)

AF:

0.133

AC:

2027

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0922

AC:

320

AN:

3472

East Asian (EAS)

AF:

0.0727

AC:

376

AN:

5174

South Asian (SAS)

AF:

0.0681

AC:

329

AN:

4828

European-Finnish (FIN)

AF:

0.115

AC:

1221

AN:

10600

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10776

AN:

67956

Other (OTH)

AF:

0.160

AC:

337

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

989

1977

2966

3954

4943

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:

0.151

Hom.:

218

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

-0.82

CADD

Benign

5.0

(source)

DANN

Benign

0.72

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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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