Variant chr3-138946187-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_023067.4(FOXL2):c.536C>G(p.Ala179Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,488,784 control chromosomes in the GnomAD database, including 5,631 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2760 hom., cov: 33)

Exomes 𝑓: 0.033 ( 2871 hom. )

Consequence

FOXL2
NM_023067.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.759

Variant links:

Genes affected

FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

FOXL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034596026).

BP6

Variant 3-138946187-G-C is Benign according to our data. Variant chr3-138946187-G-C is described in ClinVar as [Benign]. Clinvar id is 261662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2	NM_023067.4 linkuse as main transcript	c.536C>G	p.Ala179Gly	missense_variant	1/1	ENST00000648323.1	NP_075555.1	P58012Q53ZD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 linkuse as main transcript	c.536C>G	p.Ala179Gly	missense_variant	1/1		NM_023067.4	ENSP00000497217.1		P58012

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18681

AN:

151600

Hom.:

2748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.0301

Gnomad SAS

AF:

0.0859

Gnomad FIN

AF:

0.0627

Gnomad MID

AF:

0.0625

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0957

GnomAD3 exomes

AF:

0.0458

AC:

4117

AN:

89912

Hom.:

282

AF XY:

0.0492

AC XY:

2512

AN XY:

51022

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.0146

Gnomad SAS exome

AF:

0.0882

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0445

GnomAD4 exome

AF:

0.0329

AC:

44026

AN:

1337072

Hom.:

2871

Cov.:

AF XY:

0.0341

AC XY:

22516

AN XY:

659490

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.0315

Gnomad4 ASJ exome

AF:

0.0237

Gnomad4 EAS exome

AF:

0.0754

Gnomad4 SAS exome

AF:

0.0878

Gnomad4 FIN exome

AF:

0.0522

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0484

GnomAD4 genome

AF:

0.124

AC:

18749

AN:

151712

Hom.:

2760

Cov.:

AF XY:

0.122

AC XY:

9052

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.0545

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.0302

Gnomad4 SAS

AF:

0.0858

Gnomad4 FIN

AF:

0.0627

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0224

Hom.:

TwinsUK

AF:

0.0197

AC:

ALSPAC

AF:

0.0158

AC:

ExAC

AF:

0.0496

AC:

1527

Asia WGS

AF:

0.0830

AC:

289

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Blepharophimosis, ptosis, and epicanthus inversus syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.48

.;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.43

.;N

REVEL

Benign

0.22

Sift

Benign

0.25

.;T

Sift4G

Benign

0.34

.;T

Polyphen

0.83

P;P

Vest4

0.041

ClinPred

0.014

GERP RS

4.0

Varity_R

0.19

gMVP

0.31

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