Genetic Variant NM_004473.4:c.514_537delGCCGCCGCCGCCGCCGCCGCCGCC (chr9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCC-A) – 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.514_537delGCCGCCGCCGCCGCCGCCGCCGCC(p.Ala172_Ala179del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000156 in 1,219,952 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A172A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

FOXE1
NM_004473.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004473.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4 link	c.514_537delGCCGCCGCCGCCGCCGCCGCCGCC	p.Ala172_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.514_537delGCCGCCGCCGCCGCCGCCGCCGCC	p.Ala172_Ala179del	conservative_inframe_deletion	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3		O00358

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

144856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1075096

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

518062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21398

American (AMR)

AF:

0.00

AC:

AN:

7872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12636

East Asian (EAS)

AF:

0.00

AC:

AN:

23844

South Asian (SAS)

AF:

0.000158

AC:

AN:

25278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25218

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

2850

European-Non Finnish (NFE)

AF:

0.00000984

AC:

AN:

914396

Other (OTH)

AF:

0.0000240

AC:

AN:

41604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.697

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:

0.0000207

AC:

AN:

144856

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40082

American (AMR)

AF:

0.00

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:

0.000212

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:

0.0000307

AC:

AN:

65142

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=153/47

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

Computational scores

Splicing

Publications

Other links and lift over