Variant 9-97854739-C-T 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.825C>T(p.Ser275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,456,554 control chromosomes in the GnomAD database, including 282,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30736 hom., cov: 34)

Exomes 𝑓: 0.62 ( 251846 hom. )

Consequence

FOXE1
NM_004473.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.67

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-97854739-C-T is Benign according to our data. Variant chr9-97854739-C-T is described in ClinVar as [Benign]. Clinvar id is 95098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97854739-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 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.825C>T	p.Ser275=	synonymous_variant	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5 linkuse as main transcript	c.825C>T	p.Ser275=	synonymous_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96098

AN:

151754

Hom.:

30711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.628

GnomAD3 exomes

AF:

0.672

AC:

40853

AN:

60772

Hom.:

13965

AF XY:

0.667

AC XY:

22521

AN XY:

33768

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.898

Gnomad SAS exome

AF:

0.651

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.619

AC:

807716

AN:

1304692

Hom.:

251846

Cov.:

AF XY:

0.619

AC XY:

395965

AN XY:

639986

show subpopulations

Gnomad4 AFR exome

AF:

0.668

Gnomad4 AMR exome

AF:

0.679

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.878

Gnomad4 SAS exome

AF:

0.622

Gnomad4 FIN exome

AF:

0.639

Gnomad4 NFE exome

AF:

0.611

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.633

AC:

96157

AN:

151862

Hom.:

30736

Cov.:

AF XY:

0.638

AC XY:

47349

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.662

Gnomad4 AMR

AF:

0.651

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.885

Gnomad4 SAS

AF:

0.633

Gnomad4 FIN

AF:

0.640

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.621

Hom.:

3236

Bravo

AF:

0.637

Asia WGS

AF:

0.716

AC:

2471

AN:

3446

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:1

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

-0.80

CADD

Benign

1.4

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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