1-47416825-C-T

Position:

chr1-47416825-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

LINC01389 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 193357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-47416825-C-T is described in Lovd as [Benign]. Variant chr1-47416825-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
FOXE3	NM_012186.3 linkuse as main transcript	c.510C>T	p.Ala170Ala	synonymous_variant	1/1	ENST00000335071.4	NP_036318.1
LINC01389	NR_126355.1 linkuse as main transcript	n.29-6924G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXE3	ENST00000335071.4 linkuse as main transcript	c.510C>T	p.Ala170Ala	synonymous_variant	1/1	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

GnomAD3 exomes

AF:

0.349

AC:

63170

AN:

181088

Hom.:

10887

AF XY:

0.356

AC XY:

36240

AN XY:

101672

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 SAS exome

AF:

0.417

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

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.304

AC:

45636

AN:

150098

Hom.:

7221

Cov.:

AF XY:

0.301

AC XY:

22105

AN XY:

73330

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.202

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.303

Hom.:

2229

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

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Nov 17, 2022

- -

Congenital primary aphakia;C1862839:Anterior segment dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital primary aphakia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 22, 2021

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

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

DANN

Benign

0.97

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