rs1443435

Positions:

• chr9-97855301-T-C
• chr9-97855301-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004473.4(FOXE1):​c.*265T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 591,764 control chromosomes in the GnomAD database, including 119,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30788 hom., cov: 32)
  • Exomes 𝑓: 0.63 (88443 hom.)
• Consequence: FOXE1 NM_004473.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-97855301-T-C is Benign according to our data. Variant chr9-97855301-T-C is described in ClinVar as [Benign]. Clinvar id is 1260357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
FOXE1	NM_004473.4	c.*265T>C		3_prime_UTR_variant	1/1	ENST00000375123.5	NP_004464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5	c.*265T>C		3_prime_UTR_variant	1/1		NM_004473.4	ENSP00000364265	P1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96238 AN: 151898 Hom.: 30761 Cov.: 32

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: 0.639

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.629 AC: 276465 AN: 439748 Hom.: 88443 Cov.: 3 AF XY: 0.626 AC XY: 143890 AN XY: 229934

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.633 AC: 96302 AN: 152016 Hom.: 30788 Cov.: 32 AF XY: 0.638 AC XY: 47392 AN XY: 74294

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.628

Alfa AF: 0.606 Hom.: 37797

Bravo AF: 0.637

Asia WGS AF: 0.720 AC: 2506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.88
CADD	Benign	7.4
DANN	Benign	0.59

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: rs1443435; hg19: chr9-100617583; COSMIC: COSV64300103;