Variant rs2394882 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.817-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,609,460 control chromosomes in the GnomAD database, including 360,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 36757 hom., cov: 33)

Exomes 𝑓: 0.66 ( 323632 hom. )

Consequence

POU5F1
NM_002701.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.05026

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
POU5F1	NM_002701.6 linkuse as main transcript	c.817-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000259915.13
POU5F1	NM_001173531.3 linkuse as main transcript	c.307-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
POU5F1	NM_001285986.2 linkuse as main transcript	c.229-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
POU5F1	NM_203289.6 linkuse as main transcript	c.307-5T>G	splice_region_variant, 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.817-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002701.6	P1	Q01860-1

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104940

AN:

151924

Hom.:

36727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.697

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.642

AC:

154716

AN:

240940

Hom.:

50121

AF XY:

0.640

AC XY:

83985

AN XY:

131290

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.665

AC:

968539

AN:

1457418

Hom.:

323632

Cov.:

AF XY:

0.661

AC XY:

479421

AN XY:

724794

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.718

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.583

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.691

AC:

105019

AN:

152042

Hom.:

36757

Cov.:

AF XY:

0.685

AC XY:

50868

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.568

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.676

Hom.:

54998

Bravo

AF:

0.705

Asia WGS

AF:

0.665

AC:

2310

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.050

dbscSNV1_RF

Benign

0.28

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