chr3-138945652-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_023067.4(FOXL2):c.1071T>C(p.His357His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,606,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

FOXL2
NM_023067.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.66

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

blepharophimosis, ptosis, and epicanthus inversus syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
premature ovarian failure 3
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

FOXL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-138945652-A-G is Benign according to our data. Variant chr3-138945652-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 435242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.66 with no splicing effect.

BS2

High AC in GnomAd4 at 81 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2	NM_023067.4 link	c.1071T>C	p.His357His	synonymous_variant	Exon 1 of 1	ENST00000648323.1	NP_075555.1	P58012Q53ZD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 link	c.1071T>C	p.His357His	synonymous_variant	Exon 1 of 1		NM_023067.4	ENSP00000497217.1		P58012

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000544

AC:

132

AN:

242766

AF XY:

0.000557

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.00364

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.000623

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000467

AC:

679

AN:

1453988

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

342

AN XY:

722772

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33324

American (AMR)

AF:

0.000493

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00323

AC:

AN:

26018

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39506

South Asian (SAS)

AF:

0.000105

AC:

AN:

85830

European-Finnish (FIN)

AF:

0.0000584

AC:

AN:

51394

Middle Eastern (MID)

AF:

0.00244

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000447

AC:

495

AN:

1107616

Other (OTH)

AF:

0.000750

AC:

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000532

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41556

American (AMR)

AF:

0.000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000530

AC:

AN:

67970

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000710

Hom.:

Bravo

AF:

0.000514

EpiCase

AF:

0.00120

EpiControl

AF:

0.00125

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FOXL2: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 05, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

FOXL2-related disorder

Benign:1

Mar 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.8

(source)

DANN

Benign

0.59

PhyloP100

1.7

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over