9-97853784-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.-131G>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 0.625 in 847,778 control chromosomes in the GnomAD database, including 166,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30774 hom., cov: 34)
  • Exomes 𝑓: 0.62 (136195 hom.)
• Consequence: FOXE1 NM_004473.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.249

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 9-97853784-G-C is Benign according to our data. Variant chr9-97853784-G-C is described in ClinVar as [Benign]. Clinvar id is 1294056.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.-131G>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.-131G>C		5_prime_UTR_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96219 AN: 151936 Hom.: 30749 Cov.: 34

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.885

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: 0.623 AC: 433223 AN: 695732 Hom.: 136195 Cov.: 9 AF XY: 0.622 AC XY: 208981 AN XY: 335828

Gnomad4 AFR exome AF: 0.672

Gnomad4 AMR exome AF: 0.644

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.633 AC: 96278 AN: 152046 Hom.: 30774 Cov.: 34 AF XY: 0.638 AC XY: 47403 AN XY: 74346

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.629

Alfa AF: 0.620 Hom.: 3649

Bravo AF: 0.637

Asia WGS AF: 0.718 AC: 2494 AN: 3468

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.4
Dann	Benign	0.73

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: rs1867280; hg19: chr9-100616066;