Variant rs13274084 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.640A>G(p.Asn214Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,608,496 control chromosomes in the GnomAD database, including 11,982 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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 0.093 ( 837 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11145 hom. )

Consequence

POU5F1B
NM_001159542.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.505

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:

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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 (MetaRNN=0.0014190674).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 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.640A>G	p.Asn214Asp	missense_variant	1/1	ENST00000696633.1	NP_001153014.1	Q06416
POU5F1B	NM_001395745.1 linkuse as main transcript	c.640A>G	p.Asn214Asp	missense_variant	2/2		NP_001382674.1
CASC8	NR_117100.1 linkuse as main transcript	n.1176+4323T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1 linkuse as main transcript	c.640A>G	p.Asn214Asp	missense_variant	1/1		NM_001159542.3	ENSP00000512769.1		Q06416

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

14101

AN:

152042

Hom.:

837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0802

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0622

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.108

AC:

25886

AN:

238938

Hom.:

1728

AF XY:

0.109

AC XY:

14068

AN XY:

128606

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.0563

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.0665

Gnomad SAS exome

AF:

0.0675

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.119

AC:

173375

AN:

1456336

Hom.:

11145

Cov.:

113

AF XY:

0.118

AC XY:

85376

AN XY:

723812

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.0594

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.0784

Gnomad4 SAS exome

AF:

0.0699

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0927

AC:

14100

AN:

152160

Hom.:

837

Cov.:

AF XY:

0.0932

AC XY:

6929

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.0799

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.0624

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.124

Hom.:

409

Bravo

AF:

0.0843

TwinsUK

AF:

0.118

AC:

438

ALSPAC

AF:

0.120

AC:

462

ExAC

AF:

0.106

AC:

12908

Asia WGS

AF:

0.0550

AC:

198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.24

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.015

.;D

Polyphen

0.0020

B;B

Vest4

0.024

MPC

0.044

ClinPred

0.017

GERP RS

-2.3

Varity_R

0.30

gMVP

0.17

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