Genetic Variant POU5F1:p.Ser7Ser (chr6-31170600-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002701.6(POU5F1):c.21G>A(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,556,262 control chromosomes in the GnomAD database, including 147,317 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 0.43 ( 14081 hom., cov: 33)

Exomes 𝑓: 0.43 ( 133236 hom. )

Consequence

POU5F1
NM_002701.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6 link	c.21G>A	p.Ser7Ser	synonymous_variant	Exon 1 of 5	ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POU5F1	ENST00000259915.13 link	c.21G>A	p.Ser7Ser	synonymous_variant	Exon 1 of 5	1	NM_002701.6	ENSP00000259915.7	Q01860-1
POU5F1	ENST00000441888.7 link	c.-183-4553G>A		intron_variant	Intron 1 of 4	1		ENSP00000389359.2	F2Z381
POU5F1	ENST00000461401.1 link	n.59G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65198

AN:

151892

Hom.:

14076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.399

AC:

64544

AN:

161740

Hom.:

13086

AF XY:

0.397

AC XY:

34813

AN XY:

87628

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.355

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.433

AC:

608324

AN:

1404252

Hom.:

133236

Cov.:

AF XY:

0.430

AC XY:

298289

AN XY:

693424

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.385

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.429

AC:

65225

AN:

152010

Hom.:

14081

Cov.:

AF XY:

0.424

AC XY:

31505

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.457

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.430

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.416

Hom.:

4346

Bravo

AF:

0.437

Asia WGS

AF:

0.397

AC:

1379

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.7

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over