dbSNP rs17197199: POU5F1:c.-183-4648G>A (chr6-31170695-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000441888.7(POU5F1):c.-183-4648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,466,142 control chromosomes in the GnomAD database, including 2,348 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 0.072 ( 667 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1681 hom. )

Consequence

POU5F1
ENST00000441888.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441888.7. 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.-75G>A		upstream_gene	N/A	NP_002692.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POU5F1	ENST00000441888.7	TSL:1	c.-183-4648G>A	intron	N/A	ENSP00000389359.2	F2Z381
POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.-75G>A	upstream_gene	N/A	ENSP00000259915.7	Q01860-1
POU5F1	ENST00000461401.1	TSL:1	n.-37G>A	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

10964

AN:

152084

Hom.:

665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0709

GnomAD4 exome

AF:

0.0368

AC:

48416

AN:

1313938

Hom.:

1681

Cov.:

AF XY:

0.0365

AC XY:

23332

AN XY:

638742

show subpopulations

African (AFR)

AF:

0.163

AC:

4732

AN:

28962

American (AMR)

AF:

0.0334

AC:

802

AN:

24032

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

445

AN:

19746

East Asian (EAS)

AF:

0.183

AC:

6427

AN:

35030

South Asian (SAS)

AF:

0.0367

AC:

2419

AN:

65894

European-Finnish (FIN)

AF:

0.0584

AC:

2551

AN:

43674

Middle Eastern (MID)

AF:

0.0372

AC:

138

AN:

3706

European-Non Finnish (NFE)

AF:

0.0271

AC:

28173

AN:

1038676

Other (OTH)

AF:

0.0503

AC:

2729

AN:

54218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2717

5435

8152

10870

13587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1276

2552

3828

5104

6380

<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:

0.0721

AC:

10975

AN:

152204

Hom.:

667

Cov.:

AF XY:

0.0728

AC XY:

5422

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.158

AC:

6557

AN:

41508

American (AMR)

AF:

0.0403

AC:

617

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3470

East Asian (EAS)

AF:

0.166

AC:

859

AN:

5166

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4814

European-Finnish (FIN)

AF:

0.0528

AC:

561

AN:

10628

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0283

AC:

1926

AN:

68002

Other (OTH)

AF:

0.0716

AC:

151

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

482

964

1445

1927

2409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0453

Hom.:

431

Bravo

AF:

0.0775

Asia WGS

AF:

0.115

AC:

398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.6

PromoterAI

-0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over