Genetic Variant FOXE1:p.Ala177_Ala179dup (chr9-97854418-A-AGCCGCCGCC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_004473.4(FOXE1):c.529_537dupGCCGCCGCC(p.Ala177_Ala179dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000061 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXE1
NM_004473.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Laboratory for Molecular Medicine, G2P, Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

FOXE1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004473.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004473.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE1	NM_004473.4	MANE Select	c.529_537dupGCCGCCGCC	p.Ala177_Ala179dup	conservative_inframe_insertion	Exon 1 of 1	NP_004464.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE1	ENST00000375123.5	TSL:6 MANE Select	c.529_537dupGCCGCCGCC	p.Ala177_Ala179dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000364265.3	O00358

Frequencies

GnomAD3 genomes

AF:

0.0000828

AC:

AN:

144856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000998

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000683

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000107

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000614

AC:

AN:

1075090

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

518056

show subpopulations

African (AFR)

AF:

0.0000467

AC:

AN:

21398

American (AMR)

AF:

0.00

AC:

AN:

7872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12636

East Asian (EAS)

AF:

0.0000419

AC:

AN:

23844

South Asian (SAS)

AF:

0.00

AC:

AN:

25278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2850

European-Non Finnish (NFE)

AF:

0.0000667

AC:

AN:

914390

Other (OTH)

AF:

0.0000721

AC:

AN:

41604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000828

AC:

AN:

144856

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

70486

show subpopulations

African (AFR)

AF:

0.0000998

AC:

AN:

40082

American (AMR)

AF:

0.0000683

AC:

AN:

14646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4796

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.000107

AC:

AN:

65142

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00

Hom.:

Bravo

AF:

0.000117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over