Variant 9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_004473.4(FOXE1):c.535_537dup(p.Ala179dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. A168A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 22 hom., cov: 0)

Exomes 𝑓: 0.012 ( 57 hom. )

Consequence

FOXE1
NM_004473.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:2

Conservation

PhyloP100: 2.56

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004473.4

BP6

Variant 9-97854418-A-AGCC is Benign according to our data. Variant chr9-97854418-A-AGCC is described in ClinVar as [Benign]. Clinvar id is 1284456.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0174 (2523/144948) while in subpopulation AMR AF= 0.0222 (326/14664). AF 95% confidence interval is 0.0202. There are 22 homozygotes in gnomad4. There are 1307 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXE1	NM_004473.4 linkuse as main transcript	c.535_537dup	p.Ala179dup	inframe_insertion	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5 linkuse as main transcript	c.535_537dup	p.Ala179dup	inframe_insertion	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2523

AN:

144848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.0336

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00616

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0203

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.0214

GnomAD3 exomes

AF:

0.00295

AC:

AN:

12212

Hom.:

AF XY:

0.00254

AC XY:

AN XY:

7494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0124

AC:

13302

AN:

1073494

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

6298

AN XY:

517268

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.00930

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00526

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0174

AC:

2523

AN:

144948

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1307

AN XY:

70600

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00637

Gnomad4 FIN

AF:

0.0207

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over