chr9-97854412-TGCCGCAGCCGCC-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2
The NM_004473.4(FOXE1):c.504_515del(p.Ala176_Ala179del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,192,314 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.011 ( 18 hom., cov: 0)
Exomes 𝑓: 0.0064 ( 37 hom. )
Consequence
FOXE1
NM_004473.4 inframe_deletion
NM_004473.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.56
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 -11 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_004473.4
BP6
?
Variant 9-97854412-TGCCGCAGCCGCC-T is Benign according to our data. Variant chr9-97854412-TGCCGCAGCCGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044967.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-97854412-TGCCGCAGCCGCC-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.011 (1035/94260) while in subpopulation AMR AF= 0.0228 (218/9582). AF 95% confidence interval is 0.0203. There are 18 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 18 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXE1 | NM_004473.4 | c.504_515del | p.Ala176_Ala179del | inframe_deletion | 1/1 | ENST00000375123.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXE1 | ENST00000375123.5 | c.504_515del | p.Ala176_Ala179del | inframe_deletion | 1/1 | NM_004473.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0110 AC: 1034AN: 94190Hom.: 18 Cov.: 0
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GnomAD3 exomes AF: 0.0106 AC: 509AN: 47978Hom.: 7 AF XY: 0.0106 AC XY: 308AN XY: 28938
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GnomAD4 exome AF: 0.00642 AC: 7054AN: 1098054Hom.: 37 AF XY: 0.00651 AC XY: 3482AN XY: 534802
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GnomAD4 genome ? AF: 0.0110 AC: 1035AN: 94260Hom.: 18 Cov.: 0 AF XY: 0.0117 AC XY: 526AN XY: 45066
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FOXE1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 07, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at