dbSNP rs7002225: POU5F1B:p.Glu238Lys (chr8-127416578-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001159542.3(POU5F1B):c.712G>A(p.Glu238Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POU5F1B
NM_001159542.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.08

Publications

21 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
POU5F1B	NM_001159542.3 link	c.712G>A	p.Glu238Lys	missense_variant	Exon 1 of 1	ENST00000696633.1	NP_001153014.1
POU5F1B	NM_001395745.1 link	c.712G>A	p.Glu238Lys	missense_variant	Exon 2 of 2		NP_001382674.1
CASC8	NR_117100.1 link	n.1176+4251C>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.712G>A	p.Glu238Lys	missense_variant	Exon 1 of 1		NM_001159542.3	ENSP00000512769.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000207

AC:

AN:

1450444

Hom.:

Cov.:

123

AF XY:

0.00000139

AC XY:

AN XY:

720354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.00

AC:

AN:

42858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39474

South Asian (SAS)

AF:

0.00

AC:

AN:

84462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105894

Other (OTH)

AF:

0.00

AC:

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000658

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41328

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

4677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D

Eigen

Benign

-0.017

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Benign

1.3

L;L

PhyloP100

7.1

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.8

.;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0030

.;D

Polyphen

1.0

D;D

Vest4

0.18

MutPred

0.44

Gain of MoRF binding (P = 0.0252);Gain of MoRF binding (P = 0.0252);

MVP

0.59

MPC

0.22

ClinPred

1.0

GERP RS

0.20

Varity_R

0.69

gMVP

0.58

Mutation Taster

=80/20

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over