Variant 6-31166166-C-A 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.-224G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,605,810 control chromosomes in the GnomAD database, including 359,770 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 0.69 ( 36761 hom., cov: 32)

Exomes 𝑓: 0.66 ( 323009 hom. )

Consequence

POU5F1
NM_203289.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.495

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=-0.79).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6 linkuse as main transcript	c.406-119G>T		intron_variant		ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13 linkuse as main transcript	c.406-119G>T		intron_variant		1	NM_002701.6	ENSP00000259915.7		Q01860-1

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104957

AN:

151930

Hom.:

36731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.646

AC:

152795

AN:

236422

Hom.:

49611

AF XY:

0.644

AC XY:

82612

AN XY:

128280

show subpopulations

Gnomad AFR exome

AF:

0.792

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.654

Gnomad SAS exome

AF:

0.579

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.665

AC:

966642

AN:

1453762

Hom.:

323009

Cov.:

AF XY:

0.662

AC XY:

478343

AN XY:

722684

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.718

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.583

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.691

AC:

105036

AN:

152048

Hom.:

36761

Cov.:

AF XY:

0.685

AC XY:

50877

AN XY:

74318

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:

0.569

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.670

Hom.:

45806

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

-0.79

CADD

Benign

DANN

Benign

0.83

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