dbSNP rs6998061: POU5F1B:p.Gly176Glu (chr8-127416393-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

31 publications found

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:45129): (cancer susceptibility 8)

CASC8 links:

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

PCAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POU5F1B	NM_001159542.3 link	c.527G>A	p.Gly176Glu	missense_variant	Exon 1 of 1	ENST00000696633.1	NP_001153014.1	Q06416
POU5F1B	NM_001395745.1 link	c.527G>A	p.Gly176Glu	missense_variant	Exon 2 of 2		NP_001382674.1
CASC8	NR_117100.1 link	n.1176+4436C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1 link	c.527G>A	p.Gly176Glu	missense_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.403

AC:

95840

AN:

237892

AF XY:

0.412

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 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

African (AFR)

AF:

0.133

AC:

4451

AN:

33352

American (AMR)

AF:

0.368

AC:

16053

AN:

43614

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9188

AN:

25990

East Asian (EAS)

AF:

0.572

AC:

22641

AN:

39590

South Asian (SAS)

AF:

0.481

AC:

41015

AN:

85248

European-Finnish (FIN)

AF:

0.409

AC:

21667

AN:

53024

Middle Eastern (MID)

AF:

0.343

AC:

1969

AN:

5736

European-Non Finnish (NFE)

AF:

0.416

AC:

460563

AN:

1107966

Other (OTH)

AF:

0.402

AC:

24190

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

27262

54524

81786

109048

136310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14152

28304

42456

56608

70760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.345

AC:

52415

AN:

152018

Hom.:

10405

Cov.:

AF XY:

0.351

AC XY:

26060

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.146

AC:

6072

AN:

41478

American (AMR)

AF:

0.386

AC:

5898

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1237

AN:

3470

East Asian (EAS)

AF:

0.537

AC:

2758

AN:

5140

South Asian (SAS)

AF:

0.472

AC:

2271

AN:

4816

European-Finnish (FIN)

AF:

0.419

AC:

4426

AN:

10562

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28558

AN:

67956

Other (OTH)

AF:

0.361

AC:

763

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1646

3292

4938

6584

8230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.393

Hom.:

7031

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

(source)

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

PhyloP100

5.2

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

Mutation Taster

=72/28

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over