9-97853632-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004473.4(FOXE1):c.-283A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 343,252 control chromosomes in the GnomAD database, including 69,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30797 hom., cov: 33)
  • Exomes 𝑓: 0.63 (38383 hom.)
• Consequence: FOXE1 NM_004473.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-97853632-A-G is Benign according to our data. Variant chr9-97853632-A-G is described in ClinVar as [Benign]. Clinvar id is 1297302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXE1	NM_004473.4	c.-283A>G		5_prime_UTR_variant	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5	c.-283A>G		5_prime_UTR_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96259 AN: 151980 Hom.: 30772 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.627 AC: 119889 AN: 191158 Hom.: 38383 Cov.: 2 AF XY: 0.624 AC XY: 61126 AN XY: 97906

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.633 AC: 96319 AN: 152094 Hom.: 30797 Cov.: 33 AF XY: 0.638 AC XY: 47411 AN XY: 74348

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.628

Alfa AF: 0.623 Hom.: 5960

Bravo AF: 0.637

Asia WGS AF: 0.719 AC: 2499 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

This variant is associated with the following publications: (PMID: 22282540, 19730683, 26202972, 31395865) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.4
Dann	Benign	0.41

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: rs1867277; hg19: chr9-100615914;