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GeneBe

9-97854193-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004473.4(FOXE1):c.279C>T(p.Asn93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,114 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

FOXE1
NM_004473.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0110
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-97854193-C-T is Benign according to our data. Variant chr9-97854193-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659340.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-97854193-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.011 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXE1NM_004473.4 linkuse as main transcriptc.279C>T p.Asn93= synonymous_variant 1/1 ENST00000375123.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXE1ENST00000375123.5 linkuse as main transcriptc.279C>T p.Asn93= synonymous_variant 1/1 NM_004473.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00115
AC:
174
AN:
151874
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.00181
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00103
AC:
259
AN:
250412
Hom.:
1
AF XY:
0.00102
AC XY:
138
AN XY:
135724
show subpopulations
Gnomad AFR exome
AF:
0.000496
Gnomad AMR exome
AF:
0.000666
Gnomad ASJ exome
AF:
0.000299
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000686
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.00170
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.00190
AC:
2772
AN:
1461130
Hom.:
7
Cov.:
31
AF XY:
0.00190
AC XY:
1379
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.000761
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000916
Gnomad4 FIN exome
AF:
0.000132
Gnomad4 NFE exome
AF:
0.00227
Gnomad4 OTH exome
AF:
0.00167
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00114
AC:
174
AN:
151984
Hom.:
2
Cov.:
33
AF XY:
0.00110
AC XY:
82
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00181
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00162
Hom.:
1
Bravo
AF:
0.00151
EpiCase
AF:
0.00218
EpiControl
AF:
0.00196

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022FOXE1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
13
Dann
Benign
0.97

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.

Other links and lift over

dbSNP: rs150571747; hg19: chr9-100616475; API