Variant chr8-127416393-G-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_001159542.3(POU5F1B):c.527G>A(p.Gly176Glu) variant causes a missense change. The variant allele was found at a frequency of 0.407 in 1,606,718 control chromosomes in the GnomAD database, including 137,368 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 10405 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126963 hom. )

Consequence

POU5F1B
NM_001159542.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

POU5F1B links:

CASC8 (HGNC:):

CASC8 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 (MetaRNN=0.0051745176).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1B	NM_001159542.3 linkuse as main transcript	c.527G>A	p.Gly176Glu	missense_variant	1/1	ENST00000696633.1	NP_001153014.1	Q06416
POU5F1B	NM_001395745.1 linkuse as main transcript	c.527G>A	p.Gly176Glu	missense_variant	2/2		NP_001382674.1
CASC8	NR_117100.1 linkuse as main transcript	n.1176+4436C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1 linkuse as main transcript	c.527G>A	p.Gly176Glu	missense_variant	1/1		NM_001159542.3	ENSP00000512769.1		Q06416

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52410

AN:

151898

Hom.:

10401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.356

GnomAD3 exomes

AF:

0.403

AC:

95840

AN:

237892

Hom.:

19870

AF XY:

0.412

AC XY:

52866

AN XY:

128242

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.506

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.414

AC:

601737

AN:

1454700

Hom.:

126963

Cov.:

104

AF XY:

0.417

AC XY:

301125

AN XY:

722882

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.572

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.345

AC:

52415

AN:

152018

Hom.:

10405

Cov.:

AF XY:

0.351

AC XY:

26060

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.472

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.394

Hom.:

5037

Bravo

AF:

0.328

TwinsUK

AF:

0.421

AC:

1560

ALSPAC

AF:

0.402

AC:

1551

ESP6500AA

AF:

0.143

AC:

198

ESP6500EA

AF:

0.414

AC:

1316

ExAC

AF:

0.393

AC:

47719

Asia WGS

AF:

0.477

AC:

1660

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.3

.;D

REVEL

Uncertain

0.55

Sift

Benign

0.057

.;T

Sift4G

Uncertain

0.037

.;D

Polyphen

0.88

P;P

Vest4

0.18

MPC

0.26

ClinPred

0.052

GERP RS

1.1

Varity_R

0.59

gMVP

0.76

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