chr16-86510615-G-GGGCGGCGGCGGCGGGGGA

Variant names:

• chr16-86510615-G-GGGCGGCGGCGGCGGGGGA
• NM_001451.3:c.47_48insGCGGCGGCGGCGGGGGAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001451.3(FOXF1):​c.47_48insGCGGCGGCGGCGGGGGAG​(p.Gly16_Gly17insArgArgArgArgGlySer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXF1 NM_001451.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

Genes affected

FOXF1 (HGNC:3809): (forkhead box F1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF1	NM_001451.3	c.47_48insGCGGCGGCGGCGGGGGAG	p.Gly16_Gly17insArgArgArgArgGlySer	disruptive_inframe_insertion	Exon 1 of 2	ENST00000262426.6	NP_001442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF1	ENST00000262426.6	c.47_48insGCGGCGGCGGCGGGGGAG	p.Gly16_Gly17insArgArgArgArgGlySer	disruptive_inframe_insertion	Exon 1 of 2	1	NM_001451.3	ENSP00000262426.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Alveolar capillary dysplasia with pulmonary venous misalignment Uncertain:1

Mar 30, 2021

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FOXF1 NM_001451.2 exon 1 p.Gly18_Gly23dup (c.53_70dup): This variant has not been reported in the literature but is present in 1/8594 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame duplication resulting in the addition of 6 amino acids within a repeat region of glycines at position 18, and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-86544221;