Variant 6-31164879-T-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_002701.6(POU5F1):c.817-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 1,605,982 control chromosomes in the GnomAD database, including 5,373 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 0.053 ( 275 hom., cov: 34)

Exomes 𝑓: 0.077 ( 5098 hom. )

Consequence

POU5F1
NM_002701.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001850

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

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:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
POU5F1	NM_002701.6 linkuse as main transcript	c.817-12A>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000259915.13
POU5F1	NM_001173531.3 linkuse as main transcript	c.307-12A>G	splice_polypyrimidine_tract_variant, intron_variant
POU5F1	NM_001285986.2 linkuse as main transcript	c.229-12A>G	splice_polypyrimidine_tract_variant, intron_variant
POU5F1	NM_203289.6 linkuse as main transcript	c.307-12A>G	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13 linkuse as main transcript	c.817-12A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002701.6	P1	Q01860-1

Frequencies

GnomAD3 genomes

AF:

0.0526

AC:

7818

AN:

148728

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.0436

Gnomad ASJ

AF:

0.0367

Gnomad EAS

AF:

0.000989

Gnomad SAS

AF:

0.00877

Gnomad FIN

AF:

0.0469

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0801

Gnomad OTH

AF:

0.0490

GnomAD3 exomes

AF:

0.0479

AC:

11491

AN:

239650

Hom.:

420

AF XY:

0.0487

AC XY:

6364

AN XY:

130620

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0386

Gnomad EAS exome

AF:

0.00144

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0780

Gnomad OTH exome

AF:

0.0534

GnomAD4 exome

AF:

0.0771

AC:

112389

AN:

1457136

Hom.:

5098

Cov.:

AF XY:

0.0749

AC XY:

54294

AN XY:

724608

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.0372

Gnomad4 EAS exome

AF:

0.000985

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0470

Gnomad4 NFE exome

AF:

0.0916

Gnomad4 OTH exome

AF:

0.0708

GnomAD4 genome

AF:

0.0525

AC:

7820

AN:

148846

Hom.:

275

Cov.:

AF XY:

0.0496

AC XY:

3596

AN XY:

72550

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0367

Gnomad4 EAS

AF:

0.000992

Gnomad4 SAS

AF:

0.00899

Gnomad4 FIN

AF:

0.0469

Gnomad4 NFE

AF:

0.0801

Gnomad4 OTH

AF:

0.0485

Alfa

AF:

0.0659

Hom.:

144

Bravo

AF:

0.0494

Asia WGS

AF:

0.00895

AC:

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

2.1

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.022

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