Variant rs3021523 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004473.4(FOXE1):c.387T>C(p.Leu129Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 1,610,936 control chromosomes in the GnomAD database, including 473,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51150 hom., cov: 31)

Exomes 𝑓: 0.76 ( 421878 hom. )

Consequence

FOXE1
NM_004473.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0830

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-97854301-T-C is Benign according to our data. Variant chr9-97854301-T-C is described in ClinVar as [Benign]. Clinvar id is 95096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97854301-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.083 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXE1	NM_004473.4 linkuse as main transcript	c.387T>C	p.Leu129Leu	synonymous_variant	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.387T>C	p.Leu129Leu	synonymous_variant	1/1	6	NM_004473.4	ENSP00000364265.3		O00358

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

123531

AN:

151478

Hom.:

51096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.802

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.809

Gnomad NFE

AF:

0.730

Gnomad OTH

AF:

0.817

GnomAD3 exomes

AF:

0.802

AC:

199316

AN:

248542

Hom.:

80826

AF XY:

0.795

AC XY:

107286

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.946

Gnomad AMR exome

AF:

0.854

Gnomad ASJ exome

AF:

0.767

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.784

Gnomad FIN exome

AF:

0.818

Gnomad NFE exome

AF:

0.740

Gnomad OTH exome

AF:

0.782

GnomAD4 exome

AF:

0.758

AC:

1105609

AN:

1459350

Hom.:

421878

Cov.:

AF XY:

0.757

AC XY:

549784

AN XY:

726046

show subpopulations

Gnomad4 AFR exome

AF:

0.949

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.764

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.812

Gnomad4 NFE exome

AF:

0.734

Gnomad4 OTH exome

AF:

0.775

GnomAD4 genome

AF:

0.816

AC:

123634

AN:

151586

Hom.:

51150

Cov.:

AF XY:

0.823

AC XY:

60938

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.940

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.801

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.730

Gnomad4 OTH

AF:

0.819

Alfa

AF:

0.753

Hom.:

15645

Bravo

AF:

0.824

Asia WGS

AF:

0.916

AC:

3150

AN:

3438

EpiCase

AF:

0.731

EpiControl

AF:

0.742

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Bamforth-Lazarus syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.5

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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