Genetic Variant FOXF1:p.Gly20dup (chr16-86510604-A-ACGG) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001451.3(FOXF1):c.57_59dupCGG(p.Gly20dup) variant causes a disruptive 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 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.451

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

alveolar capillary dysplasia with misalignment of pulmonary veins
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

FOXF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 320786.

BS2

High AC in GnomAd4 at 253 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	NM_001451.3	MANE Select	c.57_59dupCGG	p.Gly20dup	disruptive_inframe_insertion	Exon 1 of 2	NP_001442.2	Q12946

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.57_59dupCGG	p.Gly20dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000262426.4	Q12946

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

GnomAD2 exomes

AF:

0.000811

AC:

AN:

22192

AF XY:

0.000681

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 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

African (AFR)

AF:

0.000504

AC:

AN:

23790

American (AMR)

AF:

0.000426

AC:

AN:

11738

Ashkenazi Jewish (ASJ)

AF:

0.00800

AC:

137

AN:

17124

East Asian (EAS)

AF:

0.00375

AC:

107

AN:

28568

South Asian (SAS)

AF:

0.00137

AC:

AN:

49714

European-Finnish (FIN)

AF:

0.000940

AC:

AN:

36174

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

3766

European-Non Finnish (NFE)

AF:

0.00159

AC:

1603

AN:

1007820

Other (OTH)

AF:

0.00246

AC:

123

AN:

50098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00168

AC:

253

AN:

150310

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

109

AN XY:

73432

show subpopulations

African (AFR)

AF:

0.000171

AC:

AN:

41034

American (AMR)

AF:

0.000663

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3452

East Asian (EAS)

AF:

0.00694

AC:

AN:

5046

South Asian (SAS)

AF:

0.00105

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

10212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00211

AC:

142

AN:

67442

Other (OTH)

AF:

0.00191

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00151

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Alveolar capillary dysplasia with pulmonary venous misalignment (2)

not provided (2)

FOXF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.45

Mutation Taster

=75/25

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over