Genetic Variant FOXE1:p.Ala178_Ala179del (chr9-97854418-AGCCGCC-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -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:6

Conservation

PhyloP100: 2.56

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 Lovd as [Benign]. Variant chr9-97854418-AGCCGCC-A is described in Lovd as [Likely_benign].

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

GnomAD3 exomes

AF:

0.199

AC:

2426

AN:

12212

Hom.:

732

AF XY:

0.195

AC XY:

1461

AN XY:

7494

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 SAS exome

AF:

0.109

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

Gnomad4 AFR exome

AF:

0.787

Gnomad4 AMR exome

AF:

0.626

Gnomad4 ASJ exome

AF:

0.626

Gnomad4 EAS exome

AF:

0.946

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.684

AC:

98989

AN:

144800

Hom.:

34316

Cov.:

AF XY:

0.686

AC XY:

48360

AN XY:

70522

show subpopulations

Gnomad4 AFR

AF:

0.787

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.626

Gnomad4 EAS

AF:

0.978

Gnomad4 SAS

AF:

0.685

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.689

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 22, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bamforth-Lazarus syndrome

Benign:2

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

- -

Jan 13, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCC

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