Variant 9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_004473.4(FOXE1):c.532_537del(p.Ala178_Ala179del) variant causes a 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 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/exons	MANE	UniProt
FOXE1	NM_004473.4 linkuse as main transcript	c.532_537del	p.Ala178_Ala179del	inframe_deletion	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5 linkuse as main transcript	c.532_537del	p.Ala178_Ala179del	inframe_deletion	1/1		NM_004473.4	P1

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 22, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Bamforth-Lazarus syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jan 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Feb 09, 2016	- -

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