9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_004473.4(FOXE1):c.526_537delGCCGCCGCCGCC(p.Ala176_Ala179del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00658 in 1,219,990 control chromosomes in the GnomAD database, including 40 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 0)

Exomes 𝑓: 0.0067 ( 35 hom. )

Consequence

FOXE1
NM_004473.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 4.03

Publications

21 publications found

Variant links:

Genes affected

FOXE1 (HGNC:3806): (forkhead box E1) This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with susceptibility to nonmedullary thyroid cancer-4. [provided by RefSeq, Nov 2016]

FOXE1 Gene-Disease associations (from GenCC):

Bamforth-Lazarus syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

FOXE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004473.4

BP6

Variant 9-97854418-AGCCGCCGCCGCC-A is Benign according to our data. Variant chr9-97854418-AGCCGCCGCCGCC-A is described in CliVar as Likely_benign. Clinvar id is 522197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97854418-AGCCGCCGCCGCC-A is described in CliVar as Likely_benign. Clinvar id is 522197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4 link	c.526_537delGCCGCCGCCGCC	p.Ala176_Ala179del	conservative_inframe_deletion	Exon 1 of 1	ENST00000375123.5	NP_004464.2	O00358

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5 link	c.526_537delGCCGCCGCCGCC	p.Ala176_Ala179del	conservative_inframe_deletion	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3		O00358

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

859

AN:

144844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00778

Gnomad ASJ

AF:

0.0157

Gnomad EAS

AF:

0.000626

Gnomad SAS

AF:

0.00170

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.00720

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00368

AC:

AN:

12212

AF XY:

0.00374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00922

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00667

AC:

7173

AN:

1075046

Hom.:

AF XY:

0.00675

AC XY:

3497

AN XY:

518024

show subpopulations

African (AFR)

AF:

0.00131

AC:

AN:

21396

American (AMR)

AF:

0.00864

AC:

AN:

7870

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

190

AN:

12636

East Asian (EAS)

AF:

0.000126

AC:

AN:

23842

South Asian (SAS)

AF:

0.00348

AC:

AN:

25278

European-Finnish (FIN)

AF:

0.0110

AC:

277

AN:

25218

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

2850

European-Non Finnish (NFE)

AF:

0.00674

AC:

6165

AN:

914354

Other (OTH)

AF:

0.00752

AC:

313

AN:

41602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

291

583

874

1166

1457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.00593

AC:

859

AN:

144944

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

426

AN XY:

70594

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

40194

American (AMR)

AF:

0.00778

AC:

114

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

AN:

3380

East Asian (EAS)

AF:

0.000628

AC:

AN:

4780

South Asian (SAS)

AF:

0.00170

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.0112

AC:

101

AN:

9014

Middle Eastern (MID)

AF:

0.0182

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00720

AC:

469

AN:

65132

Other (OTH)

AF:

0.0133

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FOXE1: BS2 -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Bamforth-Lazarus syndrome

Benign:1

Mar 29, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bamforth-Lazarus syndrome;C4225293:Thyroid cancer, nonmedullary, 4

Benign:1

Nov 12, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=176/24

polymorphism

(source)

Splicing

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