Variant 16-86510604-A-ACGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001451.3(FOXF1):c.57_59dup(p.Gly22dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,379,102 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

FOXF1
NM_001451.3 inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.451

Variant links:

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]

FOXF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 16-86510604-A-ACGG is Benign according to our data. Variant chr16-86510604-A-ACGG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 320786.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 253 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXF1	NM_001451.3 linkuse as main transcript	c.57_59dup	p.Gly22dup	inframe_insertion	1/2	ENST00000262426.6	NP_001442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXF1	ENST00000262426.6 linkuse as main transcript	c.57_59dup	p.Gly22dup	inframe_insertion	1/2	1	NM_001451.3	ENSP00000262426	P1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

253

AN:

150202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000663

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00691

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00211

Gnomad OTH

AF:

0.00194

GnomAD3 exomes

AF:

0.000811

AC:

AN:

22192

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

13220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00102

Gnomad EAS exome

AF:

0.00142

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.000597

Gnomad NFE exome

AF:

0.000989

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00170

AC:

2093

AN:

1228792

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1095

AN XY:

600736

show subpopulations

Gnomad4 AFR exome

AF:

0.000504

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00800

Gnomad4 EAS exome

AF:

0.00375

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.000940

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00168

AC:

253

AN:

150310

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

109

AN XY:

73432

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.000663

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00694

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00137

Gnomad4 NFE

AF:

0.00211

Gnomad4 OTH

AF:

0.00191

Bravo

AF:

0.00151

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	FOXF1: BS1, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	This variant, c.57_59dup, results in the insertion of 1 amino acid(s) of the FOXF1 protein (p.Gly23dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FOXF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 320786). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Alveolar capillary dysplasia with pulmonary venous misalignment

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

FOXF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as 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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over