Variant chr1-167415742-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002697.4(POU2F1):c.2233T>C(p.Ser745Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,614,076 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 3 hom. )

Consequence

POU2F1
NM_002697.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

POU2F1 (HGNC:9212): (POU class 2 homeobox 1) The OCT1 transcription factor was among the first identified members of the POU transcription factor family (summarized by Sturm et al., 1993 [PubMed 8314572]). Members of this family contain the POU domain, a 160-amino acid region necessary for DNA binding to the octameric sequence ATGCAAAT.[supplied by OMIM, Jul 2010]

POU2F1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076306164).

BP6

Variant 1-167415742-T-C is Benign according to our data. Variant chr1-167415742-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 708859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2F1	NM_002697.4 linkuse as main transcript	c.2233T>C	p.Ser745Pro	missense_variant	16/16	ENST00000367866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2F1	ENST00000367866.7 linkuse as main transcript	c.2233T>C	p.Ser745Pro	missense_variant	16/16	1	NM_002697.4	A1	P14859-6

Frequencies

GnomAD3 genomes

AF:

0.000947

AC:

144

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00133

AC:

335

AN:

251260

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.00370

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000608

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000800

AC:

1169

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

655

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00654

Gnomad4 EAS exome

AF:

0.00368

Gnomad4 SAS exome

AF:

0.00279

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000369

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152188

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00635

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00105

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 27, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.0053

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.0076

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.1

.;.;L;.

MutationTaster

Benign

0.73

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.84

N;N;N;N

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.31, 0.43

.;.;B;B

Vest4

0.42

MVP

0.92

MPC

1.2

ClinPred

0.035

GERP RS

4.2

Varity_R

0.16

gMVP

0.42

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over