GeneBe

rs71369530

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_004473.4(FOXE1):​c.511_537delGCCGCCGCCGCCGCCGCCGCCGCCGCC​(p.Ala171_Ala179del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000093 in 1,075,096 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

FOXE1
NM_004473.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • Bamforth-Lazarus syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_004473.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXE1NM_004473.4 linkc.511_537delGCCGCCGCCGCCGCCGCCGCCGCCGCC p.Ala171_Ala179del conservative_inframe_deletion Exon 1 of 1 ENST00000375123.5 NP_004464.2 O00358

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXE1ENST00000375123.5 linkc.511_537delGCCGCCGCCGCCGCCGCCGCCGCCGCC p.Ala171_Ala179del conservative_inframe_deletion Exon 1 of 1 6 NM_004473.4 ENSP00000364265.3 O00358

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
9.30e-7
AC:
1
AN:
1075096
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
518062
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
21398
American (AMR)
AF:
0.00
AC:
0
AN:
7872
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12636
East Asian (EAS)
AF:
0.00
AC:
0
AN:
23844
South Asian (SAS)
AF:
0.00
AC:
0
AN:
25278
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25216
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2850
European-Non Finnish (NFE)
AF:
0.00000109
AC:
1
AN:
914398
Other (OTH)
AF:
0.00
AC:
0
AN:
41604
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs71369530; hg19: chr9-100616700; API