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GeneBe

9-97854385-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004473.4(FOXE1):c.471C>T(p.Tyr157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,500,210 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00099 ( 29 hom. )

Consequence

FOXE1
NM_004473.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28
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 -15 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=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-97854385-C-T is Benign according to our data. Variant chr9-97854385-C-T is described in ClinVar as [Benign]. Clinvar id is 770583.Status of the report is criteria_provided_single_submitter, 1 stars.
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=1.28 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000993 (1341/1350478) while in subpopulation AMR AF= 0.0345 (1147/33204). AF 95% confidence interval is 0.0329. There are 29 homozygotes in gnomad4_exome. There are 591 alleles in male gnomad4_exome subpopulation. Median coverage is 51. This position pass quality control queck.
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 GnomAdExome at 23 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXE1NM_004473.4 linkuse as main transcriptc.471C>T p.Tyr157= synonymous_variant 1/1 ENST00000375123.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXE1ENST00000375123.5 linkuse as main transcriptc.471C>T p.Tyr157= synonymous_variant 1/1 NM_004473.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00170
AC:
254
AN:
149620
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0140
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00424
Gnomad SAS
AF:
0.000627
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000149
Gnomad OTH
AF:
0.00145
GnomAD3 exomes
AF:
0.00549
AC:
957
AN:
174182
Hom.:
23
AF XY:
0.00408
AC XY:
402
AN XY:
98606
show subpopulations
Gnomad AFR exome
AF:
0.000556
Gnomad AMR exome
AF:
0.0399
Gnomad ASJ exome
AF:
0.000297
Gnomad EAS exome
AF:
0.00420
Gnomad SAS exome
AF:
0.000317
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000489
Gnomad OTH exome
AF:
0.00189
GnomAD4 exome
AF:
0.000993
AC:
1341
AN:
1350478
Hom.:
29
Cov.:
51
AF XY:
0.000882
AC XY:
591
AN XY:
670246
show subpopulations
Gnomad4 AFR exome
AF:
0.000284
Gnomad4 AMR exome
AF:
0.0345
Gnomad4 ASJ exome
AF:
0.000314
Gnomad4 EAS exome
AF:
0.00234
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000199
Gnomad4 OTH exome
AF:
0.00102
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00171
AC:
256
AN:
149732
Hom.:
1
Cov.:
32
AF XY:
0.00175
AC XY:
128
AN XY:
73134
show subpopulations
Gnomad4 AFR
AF:
0.000366
Gnomad4 AMR
AF:
0.0141
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00425
Gnomad4 SAS
AF:
0.000627
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000149
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.000768
Hom.:
0
Bravo
AF:
0.00322

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
11
Dann
Benign
0.96

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: rs201181824; hg19: chr9-100616667; API