NM_004473.4:c.514_537dupGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr9-97854418-A-AGCCGCCGCCGCCGCCGCCGCCGCC
• rs71369530
• NM_004473.4:c.514_537dupGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_004473.4(FOXE1):​c.514_537dupGCCGCCGCCGCCGCCGCCGCCGCC​(p.Ala172_Ala179dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXE1 NM_004473.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 21 publications found

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]

FOXE1 Gene-Disease associations (from GenCC):

• Bamforth-Lazarus syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_004473.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4	c.514_537dupGCCGCCGCCGCCGCCGCCGCCGCC	p.Ala172_Ala179dup	conservative_inframe_insertion	Exon 1 of 1	ENST00000375123.5	NP_004464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5	c.514_537dupGCCGCCGCCGCCGCCGCCGCCGCC	p.Ala172_Ala179dup	conservative_inframe_insertion	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000744 AC: 8 AN: 1075096 Hom.: 0 Cov.: 0 AF XY: 0.00000386 AC XY: 2 AN XY: 518062

African (AFR) AF: 0.00 AC: 0 AN: 21398

American (AMR) AF: 0.00 AC: 0 AN: 7872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12636

East Asian (EAS) AF: 0.00 AC: 0 AN: 23844

South Asian (SAS) AF: 0.00 AC: 0 AN: 25278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2850

European-Non Finnish (NFE) AF: 0.00000875 AC: 8 AN: 914396

Other (OTH) AF: 0.00 AC: 0 AN: 41604

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71369530; hg19: chr9-100616700;