chr6-1390209-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001452.2(FOXF2):c.262G>A(p.Ala88Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 1,536,318 control chromosomes in the GnomAD database, including 919 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 68 hom., cov: 32)

Exomes 𝑓: 0.032 ( 851 hom. )

Consequence

FOXF2
NM_001452.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.716

Publications

7 publications found

Variant links:

COSMIC-nc: COSV107274492

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:

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

LINC01394 links:

MIR6720 (HGNC:50032): (microRNA 6720) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6720 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013511777).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0273 (4132/151344) while in subpopulation EAS AF = 0.0466 (234/5024). AF 95% confidence interval is 0.0417. There are 68 homozygotes in GnomAd4. There are 2028 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2 link	c.262G>A	p.Ala88Thr	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1	Q12947

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXF2	ENST00000645481.2 link	c.262G>A	p.Ala88Thr	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1 link	n.89+783C>T		intron_variant	Intron 1 of 2
LINC01394	ENST00000721687.1 link	n.68+783C>T		intron_variant	Intron 1 of 3
MIR6720	ENST00000611664.1 link	n.*105C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4125

AN:

151234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0177

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0475

Gnomad EAS

AF:

0.0462

Gnomad SAS

AF:

0.0412

Gnomad FIN

AF:

0.0247

Gnomad MID

AF:

0.0357

Gnomad NFE

AF:

0.0334

Gnomad OTH

AF:

0.0328

GnomAD2 exomes

AF:

0.0369

AC:

5711

AN:

154626

AF XY:

0.0371

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0480

Gnomad EAS exome

AF:

0.0543

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0444

GnomAD4 exome

AF:

0.0323

AC:

44789

AN:

1384974

Hom.:

851

Cov.:

AF XY:

0.0327

AC XY:

22421

AN XY:

685900

show subpopulations

African (AFR)

AF:

0.0154

AC:

446

AN:

28940

American (AMR)

AF:

0.0141

AC:

486

AN:

34364

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

1244

AN:

24218

East Asian (EAS)

AF:

0.0409

AC:

1421

AN:

34724

South Asian (SAS)

AF:

0.0440

AC:

3394

AN:

77192

European-Finnish (FIN)

AF:

0.0272

AC:

1257

AN:

46198

Middle Eastern (MID)

AF:

0.0530

AC:

225

AN:

4248

European-Non Finnish (NFE)

AF:

0.0318

AC:

34262

AN:

1078076

Other (OTH)

AF:

0.0360

AC:

2054

AN:

57014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

2213

4426

6639

8852

11065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1318

2636

3954

5272

6590

<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:

0.0273

AC:

4132

AN:

151344

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2028

AN XY:

73968

show subpopulations

African (AFR)

AF:

0.0131

AC:

540

AN:

41288

American (AMR)

AF:

0.0246

AC:

375

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0475

AC:

164

AN:

3454

East Asian (EAS)

AF:

0.0466

AC:

234

AN:

5024

South Asian (SAS)

AF:

0.0408

AC:

196

AN:

4802

European-Finnish (FIN)

AF:

0.0247

AC:

260

AN:

10518

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0334

AC:

2263

AN:

67716

Other (OTH)

AF:

0.0348

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0337

Hom.:

Bravo

AF:

0.0267

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.0131

AC:

ESP6500EA

AF:

0.0329

AC:

265

ExAC

AF:

0.0273

AC:

3227

Asia WGS

AF:

0.0400

AC:

139

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.21

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

N;N

PhyloP100

-0.72

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.76

.;N

REVEL

Benign

0.24

Sift

Benign

0.61

.;T

Sift4G

Benign

0.75

.;T

Polyphen

0.0

B;B

Vest4

0.012

ClinPred

0.0029

GERP RS

-5.2

Varity_R

0.027

gMVP

0.12

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over