9-97854418-AGCCGCCGCCGCCGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCC

Variant names:

• chr9-97854418-AGCCGCCGCC-A
• rs71369530
• NM_004473.4:c.529_537delGCCGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_004473.4(FOXE1):​c.529_537delGCCGCCGCC​(p.Ala177_Ala179del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000762 in 1,201,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00073 (0 hom.)
• Consequence: FOXE1 NM_004473.4 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03

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 Likely_benign. Variant got -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.529_537delGCCGCCGCC	p.Ala177_Ala179del	conservative_inframe_deletion	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.529_537delGCCGCCGCC	p.Ala177_Ala179del	conservative_inframe_deletion	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 137 AN: 144826 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000546

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.000111

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.000629

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000737 AC: 9 AN: 12212 Hom.: 0 AF XY: 0.000667 AC XY: 5 AN XY: 7494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00388

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000801

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000735 AC: 776 AN: 1056202 Hom.: 0 AF XY: 0.000820 AC XY: 417 AN XY: 508808

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00120

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.00282

Gnomad4 FIN exome AF: 0.00130

Gnomad4 NFE exome AF: 0.000579

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.000959 AC: 139 AN: 144926 Hom.: 0 Cov.: 0 AF XY: 0.000737 AC XY: 52 AN XY: 70586

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.000546

Gnomad4 ASJ AF: 0.00207

Gnomad4 EAS AF: 0.00167

Gnomad4 SAS AF: 0.00213

Gnomad4 FIN AF: 0.000111

Gnomad4 NFE AF: 0.000630

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 10, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In-frame deletion of 3 amino acids in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71369530; hg19: chr9-100616700;