rs3021523
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004473.4(FOXE1):āc.387T>Cā(p.Leu129=) 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 (ā ā ).
Frequency
Genomes: š 0.82 ( 51150 hom., cov: 31)
Exomes š: 0.76 ( 421878 hom. )
Consequence
FOXE1
NM_004473.4 synonymous
NM_004473.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0830
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]
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 | UniProt |
---|---|---|---|---|---|---|---|
FOXE1 | NM_004473.4 | c.387T>C | p.Leu129= | synonymous_variant | 1/1 | ENST00000375123.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXE1 | ENST00000375123.5 | c.387T>C | p.Leu129= | synonymous_variant | 1/1 | NM_004473.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.816 AC: 123531AN: 151478Hom.: 51096 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
123531
AN:
151478
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.802 AC: 199316AN: 248542Hom.: 80826 AF XY: 0.795 AC XY: 107286AN XY: 134992
GnomAD3 exomes
AF:
AC:
199316
AN:
248542
Hom.:
AF XY:
AC XY:
107286
AN XY:
134992
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.758 AC: 1105609AN: 1459350Hom.: 421878 Cov.: 68 AF XY: 0.757 AC XY: 549784AN XY: 726046
GnomAD4 exome
AF:
AC:
1105609
AN:
1459350
Hom.:
Cov.:
68
AF XY:
AC XY:
549784
AN XY:
726046
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.816 AC: 123634AN: 151586Hom.: 51150 Cov.: 31 AF XY: 0.823 AC XY: 60938AN XY: 74068
GnomAD4 genome
?
AF:
AC:
123634
AN:
151586
Hom.:
Cov.:
31
AF XY:
AC XY:
60938
AN XY:
74068
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3150
AN:
3438
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
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: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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at