dbSNP rs3094192: POU5F1:c.405+189G>C (chr6-31170027-C-G) – 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+189G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 870,288 control chromosomes in the GnomAD database, including 249,475 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 ( 46558 hom., cov: 31)

Exomes 𝑓: 0.75 ( 202917 hom. )

Consequence

POU5F1
NM_002701.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.575

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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6 link	c.405+189G>C		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+189G>C	intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7	Q01860-1
POU5F1	ENST00000441888.7 link	c.-183-3980G>C	intron_variant	Intron 1 of 4	1		ENSP00000389359.2	F2Z381
POU5F1	ENST00000461401.1 link	n.443+189G>C	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118580

AN:

151910

Hom.:

46519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.817

GnomAD4 exome

AF:

0.749

AC:

537636

AN:

718260

Hom.:

202917

Cov.:

AF XY:

0.747

AC XY:

273413

AN XY:

366060

show subpopulations

African (AFR)

AF:

0.851

AC:

14701

AN:

17276

American (AMR)

AF:

0.785

AC:

16501

AN:

21016

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

13145

AN:

15356

East Asian (EAS)

AF:

0.639

AC:

20656

AN:

32340

South Asian (SAS)

AF:

0.712

AC:

38016

AN:

53416

European-Finnish (FIN)

AF:

0.742

AC:

23264

AN:

31352

Middle Eastern (MID)

AF:

0.836

AC:

2083

AN:

2492

European-Non Finnish (NFE)

AF:

0.750

AC:

382601

AN:

510198

Other (OTH)

AF:

0.766

AC:

26669

AN:

34814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7039

14078

21116

28155

35194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.781

AC:

118673

AN:

152028

Hom.:

46558

Cov.:

AF XY:

0.780

AC XY:

57905

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.847

AC:

35156

AN:

41504

American (AMR)

AF:

0.805

AC:

12297

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

2990

AN:

3468

East Asian (EAS)

AF:

0.679

AC:

3487

AN:

5134

South Asian (SAS)

AF:

0.687

AC:

3309

AN:

4820

European-Finnish (FIN)

AF:

0.749

AC:

7915

AN:

10566

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.748

AC:

50806

AN:

67946

Other (OTH)

AF:

0.816

AC:

1721

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1364

2729

4093

5458

6822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.69

PhyloP100

-0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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rs3094192

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