chr9-97854418-A-AGCCGCC

Position:

• chr9-97854418-A-AGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3 BP6

The NM_004473.4(FOXE1):​c.532_537dupGCCGCC​(p.Ala178_Ala179dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: FOXE1 NM_004473.4 conservative_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.56

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 -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_004473.4
• BP6: Variant 9-97854418-A-AGCCGCC is Benign according to our data. Variant chr9-97854418-A-AGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 3061679.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXE1	NM_004473.4	c.532_537dupGCCGCC	p.Ala178_Ala179dup	conservative_inframe_insertion	1/1	ENST00000375123.5	NP_004464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5	c.532_537dupGCCGCC	p.Ala178_Ala179dup	conservative_inframe_insertion	1/1	6	NM_004473.4	ENSP00000364265.3

Frequencies

GnomAD3 genomes AF: 0.000110 AC: 16 AN: 144856 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000998

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000683

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.000498

GnomAD4 exome AF: 0.000103 AC: 111 AN: 1075070 Hom.: 0 Cov.: 0 AF XY: 0.000102 AC XY: 53 AN XY: 518048

Gnomad4 AFR exome AF: 0.000187

Gnomad4 AMR exome AF: 0.000127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000419

Gnomad4 SAS exome AF: 0.0000396

Gnomad4 FIN exome AF: 0.0000397

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.0000961

GnomAD4 genome AF: 0.000110 AC: 16 AN: 144856 Hom.: 0 Cov.: 0 AF XY: 0.0000851 AC XY: 6 AN XY: 70486

Gnomad4 AFR AF: 0.0000998

Gnomad4 AMR AF: 0.0000683

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.000498

Bravo AF: 0.000147

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FOXE1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;