Genetic Variant FOXF1:p.Glu6Gln (chr16-86510585-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001451.3(FOXF1):c.16G>C(p.Glu6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXF1
NM_001451.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Publications

0 publications found

Variant links:

Genes affected

FOXF1 (HGNC:3809): (forkhead box F1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

FOXF1 Gene-Disease associations (from GenCC):

alveolar capillary dysplasia with misalignment of pulmonary veins
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

FOXF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19216004).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	NM_001451.3	MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 1 of 2	NP_001442.2	Q12946

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 1 of 2	ENSP00000262426.4	Q12946

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

35088

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1224564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

599746

African (AFR)

AF:

0.00

AC:

AN:

23846

American (AMR)

AF:

0.00

AC:

AN:

13516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18262

East Asian (EAS)

AF:

0.00

AC:

AN:

27516

South Asian (SAS)

AF:

0.00

AC:

AN:

50894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1004036

Other (OTH)

AF:

0.00

AC:

AN:

49914

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73954

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41246

American (AMR)

AF:

0.000131

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67800

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.28

MutationAssessor

Benign

0.0

PhyloP100

2.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.15

REVEL

Benign

0.28

Sift

Benign

0.14

Sift4G

Benign

0.46

Polyphen

0.032

Vest4

0.24

MutPred

0.12

Loss of glycosylation at P5 (P = 0.1219)

MVP

0.44

ClinPred

0.19

GERP RS

3.5

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.14

gMVP

0.42

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over