NM_004473.4:c.532_537delGCCGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_004473.4(FOXE1):c.532_537delGCCGCC(p.Ala178_Ala179del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 1,218,904 control chromosomes in the GnomAD database, including 240,692 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34316 hom., cov: 0)

Exomes 𝑓: 0.62 ( 206376 hom. )

Consequence

FOXE1
NM_004473.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.56

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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004473.4

BP6

Variant 9-97854418-AGCCGCC-A is Benign according to our data. Variant chr9-97854418-AGCCGCC-A is described in CliVar as Benign. Clinvar id is 95097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97854418-AGCCGCC-A is described in CliVar as Benign. Clinvar id is 95097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4 link	c.532_537delGCCGCC	p.Ala178_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.532_537delGCCGCC	p.Ala178_Ala179del	conservative_inframe_deletion	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3		O00358

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

98926

AN:

144700

Hom.:

34290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.788

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.690

GnomAD2 exomes

AF:

0.199

AC:

2426

AN:

12212

AF XY:

0.195

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.430

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.621

AC:

667120

AN:

1074104

Hom.:

206376

AF XY:

0.619

AC XY:

320603

AN XY:

517590

show subpopulations

African (AFR)

AF:

0.787

AC:

16835

AN:

21384

American (AMR)

AF:

0.626

AC:

4911

AN:

7850

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

7898

AN:

12620

East Asian (EAS)

AF:

0.946

AC:

22542

AN:

23832

South Asian (SAS)

AF:

0.623

AC:

15719

AN:

25250

European-Finnish (FIN)

AF:

0.587

AC:

14750

AN:

25124

Middle Eastern (MID)

AF:

0.584

AC:

1661

AN:

2842

European-Non Finnish (NFE)

AF:

0.609

AC:

556084

AN:

913670

Other (OTH)

AF:

0.643

AC:

26720

AN:

41532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

9887

19773

29660

39546

49433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17510

35020

52530

70040

87550

<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:

0.684

AC:

98989

AN:

144800

Hom.:

34316

Cov.:

AF XY:

0.686

AC XY:

48360

AN XY:

70522

show subpopulations

African (AFR)

AF:

0.787

AC:

31614

AN:

40146

American (AMR)

AF:

0.684

AC:

10018

AN:

14654

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2116

AN:

3380

East Asian (EAS)

AF:

0.978

AC:

4676

AN:

4780

South Asian (SAS)

AF:

0.685

AC:

3218

AN:

4700

European-Finnish (FIN)

AF:

0.615

AC:

5539

AN:

9002

Middle Eastern (MID)

AF:

0.723

AC:

198

AN:

274

European-Non Finnish (NFE)

AF:

0.612

AC:

39834

AN:

65070

Other (OTH)

AF:

0.689

AC:

1394

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1436

2872

4308

5744

7180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 22, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Bamforth-Lazarus syndrome

Benign:2

Jan 13, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 09, 2016

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=192/8

polymorphism (auto)

(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