Variant 6-31166117-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203289.6(POU5F1):c.-175C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,613,976 control chromosomes in the GnomAD database, including 2,609 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 0.073 ( 674 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1935 hom. )

Consequence

POU5F1
NM_203289.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.758

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:

POU5F1 (HGNC:):

POU5F1 links:

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TCF19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6 linkuse as main transcript	c.406-70C>G	intron_variant		ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3
POU5F1	NM_203289.6 linkuse as main transcript	c.-175C>G	5_prime_UTR_variant	1/4		NP_976034.4	M1S623
POU5F1	NM_001285986.2 linkuse as main transcript	c.-478C>G	5_prime_UTR_variant	1/3		NP_001272915.1	F2Z381
POU5F1	NM_001173531.3 linkuse as main transcript	c.-105-70C>G	intron_variant			NP_001167002.1	M1S623

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13 linkuse as main transcript	c.406-70C>G		intron_variant		1	NM_002701.6	ENSP00000259915.7		Q01860-1

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11125

AN:

152064

Hom.:

672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0424

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0738

GnomAD3 exomes

AF:

0.0519

AC:

13028

AN:

250802

Hom.:

663

AF XY:

0.0494

AC XY:

6706

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0501

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.0381

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.0276

Gnomad OTH exome

AF:

0.0478

GnomAD4 exome

AF:

0.0379

AC:

55344

AN:

1461794

Hom.:

1935

Cov.:

AF XY:

0.0374

AC XY:

27176

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.0366

Gnomad4 FIN exome

AF:

0.0579

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0526

GnomAD4 genome

AF:

0.0732

AC:

11135

AN:

152182

Hom.:

674

Cov.:

AF XY:

0.0740

AC XY:

5507

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.0527

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0744

Alfa

AF:

0.0409

Hom.:

170

Bravo

AF:

0.0784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.39

DANN

Benign

0.46

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