9-97854418-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004473.4(FOXE1):c.504A>C(p.Ala168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,220,038 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00047 (4 hom.)
• Consequence: FOXE1 NM_004473.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-97854418-A-C is Benign according to our data. Variant chr9-97854418-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXE1	NM_004473.4	c.504A>C	p.Ala168=	synonymous_variant	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5	c.504A>C	p.Ala168=	synonymous_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 59 AN: 144854 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000849

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.000498

GnomAD3 exomes AF: 0.00762 AC: 93 AN: 12212 Hom.: 1 AF XY: 0.00774 AC XY: 58 AN XY: 7494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.0388

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00401

Gnomad FIN exome AF: 0.00423

Gnomad NFE exome AF: 0.00786

Gnomad OTH exome AF: 0.00413

GnomAD4 exome AF: 0.000465 AC: 500 AN: 1075084 Hom.: 4 Cov.: 36 AF XY: 0.000504 AC XY: 261 AN XY: 518062

Gnomad4 AFR exome AF: 0.000841

Gnomad4 AMR exome AF: 0.00241

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000870

Gnomad4 FIN exome AF: 0.000397

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.000414 AC: 60 AN: 144954 Hom.: 0 Cov.: 25 AF XY: 0.000411 AC XY: 29 AN XY: 70598

Gnomad4 AFR AF: 0.000199

Gnomad4 AMR AF: 0.000136

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000850

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000768

Gnomad4 OTH AF: 0.000493

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

FOXE1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs3021524; hg19: chr9-100616700;