Variant chr9-97854418-AGCCGCCGCCGCC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 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

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

Conservation

PhyloP100: 4.03

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

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXE1	NM_004473.4 linkuse as main transcript	c.526_537delGCCGCCGCCGCC	p.Ala176_Ala179del	conservative_inframe_deletion	1/1	ENST00000375123.5	NP_004464.2	O00358

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5 linkuse as main transcript	c.526_537delGCCGCCGCCGCC	p.Ala176_Ala179del	conservative_inframe_deletion	1/1	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

GnomAD3 exomes

AF:

0.00368

AC:

AN:

12212

Hom.:

AF XY:

0.00374

AC XY:

AN XY:

7494

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 SAS exome

AF:

0.000801

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

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00864

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00348

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.00674

Gnomad4 OTH exome

AF:

0.00752

GnomAD4 genome

AF:

0.00593

AC:

859

AN:

144944

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

426

AN XY:

70594

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.0157

Gnomad4 EAS

AF:

0.000628

Gnomad4 SAS

AF:

0.00170

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00720

Gnomad4 OTH

AF:

0.0133

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	FOXE1: BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Bamforth-Lazarus syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Mar 29, 2016

- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 12, 2021

- -

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.

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