6-1390068-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001452.2(FOXF2):​c.121G>T​(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,382,210 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 9 hom. )

Consequence

FOXF2
NM_001452.2 missense

Scores

1
1
17

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.660
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010308832).
BP6
Variant 6-1390068-G-T is Benign according to our data. Variant chr6-1390068-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045896.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 288 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FOXF2NM_001452.2 linkuse as main transcriptc.121G>T p.Ala41Ser missense_variant 1/2 ENST00000645481.2 NP_001443.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXF2ENST00000645481.2 linkuse as main transcriptc.121G>T p.Ala41Ser missense_variant 1/2 NM_001452.2 ENSP00000496415 P1

Frequencies

GnomAD3 genomes
AF:
0.00192
AC:
288
AN:
149642
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000999
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00140
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.000208
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00327
Gnomad OTH
AF:
0.00146
GnomAD3 exomes
AF:
0.00128
AC:
97
AN:
75792
Hom.:
0
AF XY:
0.00135
AC XY:
59
AN XY:
43762
show subpopulations
Gnomad AFR exome
AF:
0.00113
Gnomad AMR exome
AF:
0.000214
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000309
Gnomad NFE exome
AF:
0.00330
Gnomad OTH exome
AF:
0.000470
GnomAD4 exome
AF:
0.00322
AC:
3970
AN:
1232462
Hom.:
9
Cov.:
28
AF XY:
0.00308
AC XY:
1873
AN XY:
607400
show subpopulations
Gnomad4 AFR exome
AF:
0.000678
Gnomad4 AMR exome
AF:
0.000251
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000252
Gnomad4 NFE exome
AF:
0.00387
Gnomad4 OTH exome
AF:
0.00217
GnomAD4 genome
AF:
0.00192
AC:
288
AN:
149748
Hom.:
0
Cov.:
32
AF XY:
0.00178
AC XY:
130
AN XY:
73076
show subpopulations
Gnomad4 AFR
AF:
0.000997
Gnomad4 AMR
AF:
0.00139
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.000208
Gnomad4 NFE
AF:
0.00327
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.00357
Hom.:
0
Bravo
AF:
0.00195
ExAC
AF:
0.000372
AC:
10

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

FOXF2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 15, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
12
DANN
Benign
0.89
DEOGEN2
Benign
0.026
T;T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.26
.;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.010
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
-0.34
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
0.060
.;N
REVEL
Benign
0.17
Sift
Benign
0.65
.;T
Sift4G
Benign
0.51
.;T
Polyphen
0.0080
B;B
Vest4
0.092
MVP
0.81
ClinPred
0.0067
T
GERP RS
2.3
Varity_R
0.055
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778501522; hg19: chr6-1390303; API