Variant chr8-127416578-G-C 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.712G>C(p.Glu238Gln) variant causes a missense change. The variant allele was found at a frequency of 0.5 in 1,601,386 control chromosomes in the GnomAD database, including 204,089 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 0.45 ( 16656 hom., cov: 32)

Exomes 𝑓: 0.51 ( 187433 hom. )

Consequence

POU5F1B
NM_001159542.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.08

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.2544813E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
POU5F1B	NM_001159542.3 linkuse as main transcript	c.712G>C	p.Glu238Gln	missense_variant	1/1	ENST00000696633.1	NP_001153014.1
CASC8	NR_117100.1 linkuse as main transcript	n.1176+4251C>G		intron_variant, non_coding_transcript_variant
POU5F1B	NM_001395745.1 linkuse as main transcript	c.712G>C	p.Glu238Gln	missense_variant	2/2		NP_001382674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1 linkuse as main transcript	c.712G>C	p.Glu238Gln	missense_variant	1/1		NM_001159542.3	ENSP00000512769	P1
CASC8	ENST00000502082.5 linkuse as main transcript	n.1176+4251C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68701

AN:

151796

Hom.:

16651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.478

GnomAD3 exomes

AF:

0.505

AC:

115145

AN:

228110

Hom.:

29807

AF XY:

0.506

AC XY:

62200

AN XY:

122872

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.540

Gnomad SAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.477

Gnomad NFE exome

AF:

0.488

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.505

AC:

732668

AN:

1449472

Hom.:

187433

Cov.:

123

AF XY:

0.507

AC XY:

365255

AN XY:

719760

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.624

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.480

Gnomad4 NFE exome

AF:

0.503

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.452

AC:

68722

AN:

151914

Hom.:

16656

Cov.:

AF XY:

0.459

AC XY:

34037

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.509

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.453

Hom.:

4677

Bravo

AF:

0.449

TwinsUK

AF:

0.506

AC:

1877

ALSPAC

AF:

0.489

AC:

1885

ExAC

AF:

0.483

AC:

58326

Asia WGS

AF:

0.565

AC:

1963

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;D

Eigen

Benign

0.074

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.89

.;D

MetaRNN

Benign

0.00073

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.000041

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.8

.;D

REVEL

Uncertain

0.54

Sift

Benign

0.040

.;D

Sift4G

Uncertain

0.0040

.;D

Polyphen

1.0

D;D

Vest4

0.063

MPC

0.13

ClinPred

0.071

GERP RS

0.20

Varity_R

0.51

gMVP

0.43

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