Genetic Variant FOXF2:p.Ala41dup (chr6-1390041-C-CCCG) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_001452.2(FOXF2):c.121_123dupGCC(p.Ala41dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 1,354,102 control chromosomes in the GnomAD database, including 155 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P42P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.020 ( 39 hom., cov: 31)

Exomes 𝑓: 0.017 ( 116 hom. )

Consequence

FOXF2
NM_001452.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

FOXF2 (HGNC:3810): (forkhead box F2) FOXF2 encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster transcription factor forkhead. FOXF2 is expressed in lung and placenta, and has been shown to transcriptionally activate several lung-specific genes. [provided by RefSeq, Jul 2008]

FOXF2 links:

FOXF2-DT (HGNC:50662): (FOXF2 divergent transcript)

FOXF2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 6-1390041-C-CCCG is Benign according to our data. Variant chr6-1390041-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 3055662.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2 link	c.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2	ENST00000645481.2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1 link	n.458+38_458+40dupCGG		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1 link	n.69-818_69-816dupCGG		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1 link	n.68+948_68+950dupCGG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2 link	c.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2		NM_001452.2	ENSP00000496415.1		Q12947

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2865

AN:

145186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00225

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0895

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0236

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0164

GnomAD2 exomes

AF:

0.0318

AC:

1084

AN:

34036

AF XY:

0.0310

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0273

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0640

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0174

AC:

21024

AN:

1208818

Hom.:

116

Cov.:

AF XY:

0.0176

AC XY:

10452

AN XY:

593484

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

AC:

284

AN:

24344

Gnomad4 AMR exome

AF:

0.0132

AC:

285

AN:

21532

Gnomad4 ASJ exome

AF:

0.0131

AC:

253

AN:

19260

Gnomad4 EAS exome

AF:

0.126

AC:

2885

AN:

22958

Gnomad4 SAS exome

AF:

0.0129

AC:

759

AN:

58824

Gnomad4 FIN exome

AF:

0.0329

AC:

926

AN:

28124

Gnomad4 NFE exome

AF:

0.0151

AC:

14785

AN:

982126

Gnomad4 Remaining exome

AF:

0.0167

AC:

804

AN:

48226

Heterozygous variant carriers

834

1668

2501

3335

4169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.0197

AC:

2864

AN:

145284

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1459

AN XY:

70760

show subpopulations

Gnomad4 AFR

AF:

0.0132

AC:

0.0131592

AN:

0.0131592

Gnomad4 AMR

AF:

0.0115

AC:

0.0114903

AN:

0.0114903

Gnomad4 ASJ

AF:

0.0153

AC:

0.0153392

AN:

0.0153392

Gnomad4 EAS

AF:

0.0894

AC:

0.089404

AN:

0.089404

Gnomad4 SAS

AF:

0.0194

AC:

0.0193947

AN:

0.0193947

Gnomad4 FIN

AF:

0.0403

AC:

0.040281

AN:

0.040281

Gnomad4 NFE

AF:

0.0184

AC:

0.018363

AN:

0.018363

Gnomad4 OTH

AF:

0.0158

AC:

0.0157947

AN:

0.0157947

Heterozygous variant carriers

134

267

401

534

668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00452

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXF2-related disorder

Benign:1

Sep 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Mutation Taster

=85/15

polymorphism

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