Genetic Variant NM_001452.2:c.121_123delGCC (chr6-1390041-CCCG-C) – 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_001452.2(FOXF2):c.121_123delGCC(p.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 0.0198 in 1,247,212 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.022 ( 1 hom. )

Consequence

FOXF2
NM_001452.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

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:

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 6-1390041-CCCG-C is Benign according to our data. Variant chr6-1390041-CCCG-C is described in ClinVar as Benign. ClinVar VariationId is 3055285.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 184 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.121_123delGCC	p.Ala41del	conservative_inframe_deletion	Exon 1 of 2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1		n.458+38_458+40delCGG		intron	N/A
FOXF2-DT	NR_189294.1		n.69-818_69-816delCGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXF2	ENST00000645481.2	MANE Select	c.121_123delGCC	p.Ala41del	conservative_inframe_deletion	Exon 1 of 2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1		n.89+948_89+950delCGG		intron	N/A
LINC01394	ENST00000721687.1		n.69-818_69-816delCGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

179

AN:

145168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000350

Gnomad OTH

AF:

0.000499

GnomAD2 exomes

AF:

0.0667

AC:

2269

AN:

34036

AF XY:

0.0660

show subpopulations

Gnomad AFR exome

AF:

0.0457

Gnomad AMR exome

AF:

0.0721

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.0940

Gnomad FIN exome

AF:

0.0520

Gnomad NFE exome

AF:

0.0637

Gnomad OTH exome

AF:

0.0649

GnomAD4 exome

AF:

0.0222

AC:

24507

AN:

1101948

Hom.:

AF XY:

0.0236

AC XY:

12580

AN XY:

533458

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0239

AC:

533

AN:

22256

American (AMR)

AF:

0.0486

AC:

796

AN:

16374

Ashkenazi Jewish (ASJ)

AF:

0.0327

AC:

519

AN:

15872

East Asian (EAS)

AF:

0.0197

AC:

393

AN:

19970

South Asian (SAS)

AF:

0.0582

AC:

2727

AN:

46884

European-Finnish (FIN)

AF:

0.0383

AC:

875

AN:

22858

Middle Eastern (MID)

AF:

0.0303

AC:

AN:

3000

European-Non Finnish (NFE)

AF:

0.0192

AC:

17494

AN:

911708

Other (OTH)

AF:

0.0251

AC:

1079

AN:

43026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.262

Heterozygous variant carriers

3017

6033

9050

12066

15083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

550

1100

1650

2200

2750

<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:

0.00127

AC:

184

AN:

145264

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

70750

show subpopulations

African (AFR)

AF:

0.00333

AC:

134

AN:

40196

American (AMR)

AF:

0.00109

AC:

AN:

14704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4832

South Asian (SAS)

AF:

0.000213

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

8532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000350

AC:

AN:

65726

Other (OTH)

AF:

0.000494

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000112

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FOXF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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