chr1-47416825-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012186.3(FOXE3):c.510C>T(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,541,002 control chromosomes in the GnomAD database, including 98,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7221 hom., cov: 33)

Exomes 𝑓: 0.36 ( 91304 hom. )

Consequence

FOXE3
NM_012186.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.44

Publications

19 publications found

Variant links:

Genes affected

FOXE3 (HGNC:3808): (forkhead box E3) This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. The protein encoded functions as a lens-specific transcription factor and plays an important role in vertebrate lens formation. Mutations in this gene are associated with anterior segment mesenchymal dysgenesis and congenital primary aphakia. [provided by RefSeq, Dec 2009]

FOXE3 links:

LINC01389 (HGNC:50661): (long intergenic non-protein coding RNA 1389)

LINC01389 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-47416825-C-T is Benign according to our data. Variant chr1-47416825-C-T is described in ClinVar as Benign. ClinVar VariationId is 193357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE3	NM_012186.3 link	c.510C>T	p.Ala170Ala	synonymous_variant	Exon 1 of 1	ENST00000335071.4	NP_036318.1
LINC01389	NR_126355.1 link	n.29-6924G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE3	ENST00000335071.4 link	c.510C>T	p.Ala170Ala	synonymous_variant	Exon 1 of 1	6	NM_012186.3	ENSP00000334472.2		Q13461

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

45649

AN:

149990

Hom.:

7229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.375

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.349

AC:

63170

AN:

181088

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.360

AC:

500557

AN:

1390904

Hom.:

91304

Cov.:

AF XY:

0.362

AC XY:

250355

AN XY:

691896

show subpopulations

African (AFR)

AF:

0.244

AC:

6993

AN:

28644

American (AMR)

AF:

0.259

AC:

8873

AN:

34200

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

7918

AN:

23992

East Asian (EAS)

AF:

0.239

AC:

7880

AN:

32982

South Asian (SAS)

AF:

0.402

AC:

32059

AN:

79724

European-Finnish (FIN)

AF:

0.266

AC:

13529

AN:

50906

Middle Eastern (MID)

AF:

0.388

AC:

1583

AN:

4078

European-Non Finnish (NFE)

AF:

0.372

AC:

402054

AN:

1079540

Other (OTH)

AF:

0.346

AC:

19668

AN:

56838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

17104

34207

51311

68414

85518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12824

25648

38472

51296

64120

<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:

0.304

AC:

45636

AN:

150098

Hom.:

7221

Cov.:

AF XY:

0.301

AC XY:

22105

AN XY:

73330

show subpopulations

African (AFR)

AF:

0.235

AC:

9688

AN:

41300

American (AMR)

AF:

0.278

AC:

4196

AN:

15108

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1059

AN:

3446

East Asian (EAS)

AF:

0.202

AC:

1029

AN:

5088

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4824

European-Finnish (FIN)

AF:

0.259

AC:

2506

AN:

9668

Middle Eastern (MID)

AF:

0.355

AC:

103

AN:

290

European-Non Finnish (NFE)

AF:

0.360

AC:

24233

AN:

67384

Other (OTH)

AF:

0.297

AC:

618

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1662

3324

4986

6648

8310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.302

Hom.:

2255

Bravo

AF:

0.299

Asia WGS

AF:

0.225

AC:

777

AN:

3430

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Sep 28, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Nov 17, 2022

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital primary aphakia;C1862839:Anterior segment dysgenesis

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital primary aphakia

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital primary aphakia;C2751822:Cataract 34 multiple types;C4479235:Aortic aneurysm, familial thoracic 11, susceptibility to

Benign:1

Oct 22, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.2

(source)

DANN

Benign

0.97

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(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