9-97853378-G-C

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.-537G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,740 control chromosomes in the GnomAD database, including 51,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51399 hom., cov: 34)
  • Exomes 𝑓: 0.74 (147 hom.)
• Consequence: FOXE1 NM_004473.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337

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=-0.86).
• BP6: Variant 9-97853378-G-C is Benign according to our data. Variant chr9-97853378-G-C is described in ClinVar as [Benign]. Clinvar id is 1271089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXE1	NM_004473.4	c.-537G>C		5_prime_UTR_variant	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5	c.-537G>C		5_prime_UTR_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124088 AN: 152108 Hom.: 51343 Cov.: 34

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.819

GnomAD4 exome AF: 0.739 AC: 383 AN: 518 Hom.: 147 Cov.: 0 AF XY: 0.741 AC XY: 237 AN XY: 320

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.857

GnomAD4 genome AF: 0.816 AC: 124195 AN: 152222 Hom.: 51399 Cov.: 34 AF XY: 0.823 AC XY: 61228 AN XY: 74420

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.821

Alfa AF: 0.772 Hom.: 5715

Bravo AF: 0.824

Asia WGS AF: 0.916 AC: 3182 AN: 3474

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.0
Dann	Benign	0.61

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: rs7849497; hg19: chr9-100615660;