Genetic Variant FOXF2:p.Ala37_Ala41del (chr6-1390041-CCCGCCGCCGCCGCCG-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001452.2(FOXF2):c.109_123delGCCGCCGCCGCCGCC(p.Ala37_Ala41del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,354,798 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

FOXF2
NM_001452.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Publications

0 publications found

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:

LINC01394 (HGNC:50670): (long intergenic non-protein coding RNA 1394)

LINC01394 links:

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

FOXF2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 70 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	NM_001452.2	MANE Select	c.109_123delGCCGCCGCCGCCGCC	p.Ala37_Ala41del	conservative_inframe_deletion	Exon 1 of 2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1		n.458+26_458+40delCGGCGGCGGCGGCGG		intron	N/A
FOXF2-DT	NR_189294.1		n.69-830_69-816delCGGCGGCGGCGGCGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	ENST00000645481.2	MANE Select	c.109_123delGCCGCCGCCGCCGCC	p.Ala37_Ala41del	conservative_inframe_deletion	Exon 1 of 2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1		n.89+936_89+950delCGGCGGCGGCGGCGG		intron	N/A
LINC01394	ENST00000721687.1		n.69-830_69-816delCGGCGGCGGCGGCGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000482

AC:

AN:

145200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000206

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.000234

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000289

Gnomad OTH

AF:

0.000996

GnomAD2 exomes

AF:

0.000441

AC:

AN:

34036

AF XY:

0.000658

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000346

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000753

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00209

GnomAD4 exome

AF:

0.000290

AC:

351

AN:

1209500

Hom.:

AF XY:

0.000286

AC XY:

170

AN XY:

593856

show subpopulations

African (AFR)

AF:

0.000411

AC:

AN:

24356

American (AMR)

AF:

0.000463

AC:

AN:

21582

Ashkenazi Jewish (ASJ)

AF:

0.0000519

AC:

AN:

19286

East Asian (EAS)

AF:

0.000130

AC:

AN:

23046

South Asian (SAS)

AF:

0.000204

AC:

AN:

58902

European-Finnish (FIN)

AF:

0.000568

AC:

AN:

28176

Middle Eastern (MID)

AF:

0.000292

AC:

AN:

3424

European-Non Finnish (NFE)

AF:

0.000273

AC:

268

AN:

982484

Other (OTH)

AF:

0.000622

AC:

AN:

48244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000482

AC:

AN:

145298

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

AN XY:

70768

show subpopulations

African (AFR)

AF:

0.000473

AC:

AN:

40206

American (AMR)

AF:

0.00177

AC:

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.000207

AC:

AN:

4832

South Asian (SAS)

AF:

0.000213

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.000234

AC:

AN:

8544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000289

AC:

AN:

65732

Other (OTH)

AF:

0.000987

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=181/19

polymorphism

(source)

Splicing

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

Publications

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6-1390041-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCG

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