Variant 1-167389600-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM1BP4_StrongBP6_ModerateBS2

The NM_002697.4(POU2F1):c.826A>G(p.Thr276Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,614,126 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 12 hom. )

Consequence

POU2F1
NM_002697.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.91

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 -8 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity PO2F1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.010557413).

BP6

Variant 1-167389600-A-G is Benign according to our data. Variant chr1-167389600-A-G is described in ClinVar as [Benign]. Clinvar id is 718797.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 371 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2F1	NM_002697.4 linkuse as main transcript	c.826A>G	p.Thr276Ala	missense_variant	9/16	ENST00000367866.7	NP_002688.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2F1	ENST00000367866.7 linkuse as main transcript	c.826A>G	p.Thr276Ala	missense_variant	9/16	1	NM_002697.4	ENSP00000356840	A1	P14859-6

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

371

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00304

AC:

765

AN:

251324

Hom.:

AF XY:

0.00310

AC XY:

421

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00652

Gnomad NFE exome

AF:

0.00511

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00309

AC:

4515

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2140

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00593

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00244

AC:

371

AN:

152274

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00593

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00318

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00357

AC:

433

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00367

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

.;.;T;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.3

.;.;M;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

D;D;D;D;D

Sift4G

Benign

0.77

T;T;T;T;T

Polyphen

0.98, 0.99

.;.;D;D;.

Vest4

0.66

MVP

0.84

MPC

0.36

ClinPred

0.043

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.54

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