Genetic Variant FOXF2:p.Ala40_Ala41dup (chr6-1390041-C-CCCGCCG) – 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.118_123dupGCCGCC(p.Ala40_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 0.000644 in 1,354,840 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P42P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

FOXF2
NM_001452.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

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:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 156 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.118_123dupGCCGCC	p.Ala40_Ala41dup	conservative_inframe_insertion	Exon 1 of 2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1		n.458+35_458+40dupCGGCGG		intron	N/A
FOXF2-DT	NR_189294.1		n.69-821_69-816dupCGGCGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	ENST00000645481.2	MANE Select	c.118_123dupGCCGCC	p.Ala40_Ala41dup	conservative_inframe_insertion	Exon 1 of 2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1		n.89+945_89+950dupCGGCGG		intron	N/A
LINC01394	ENST00000721687.1		n.69-821_69-816dupCGGCGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

154

AN:

145198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000340

Gnomad ASJ

AF:

0.00147

Gnomad EAS

AF:

0.00124

Gnomad SAS

AF:

0.000639

Gnomad FIN

AF:

0.000117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.00149

GnomAD4 exome

AF:

0.000593

AC:

717

AN:

1209544

Hom.:

Cov.:

AF XY:

0.000616

AC XY:

366

AN XY:

593884

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

24356

American (AMR)

AF:

0.000417

AC:

AN:

21582

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

19288

East Asian (EAS)

AF:

0.000824

AC:

AN:

23048

South Asian (SAS)

AF:

0.000221

AC:

AN:

58916

European-Finnish (FIN)

AF:

0.0000355

AC:

AN:

28178

Middle Eastern (MID)

AF:

0.000877

AC:

AN:

3422

European-Non Finnish (NFE)

AF:

0.000587

AC:

577

AN:

982502

Other (OTH)

AF:

0.000622

AC:

AN:

48252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00107

AC:

156

AN:

145296

Hom.:

Cov.:

AF XY:

0.000933

AC XY:

AN XY:

70766

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

40206

American (AMR)

AF:

0.000272

AC:

AN:

14706

Ashkenazi Jewish (ASJ)

AF:

0.00147

AC:

AN:

3392

East Asian (EAS)

AF:

0.00124

AC:

AN:

4832

South Asian (SAS)

AF:

0.000639

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.000117

AC:

AN:

8546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00105

AC:

AN:

65730

Other (OTH)

AF:

0.00197

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000223

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=85/15

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-CCCGCCGCCGCCGCCGCCGCCGCCGCCG

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