NM_001452.2:c.121G>T

Variant names:

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

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]

FOXF2 links:

FOXF2-DT (HGNC:50662): (FOXF2 divergent transcript)

FOXF2-DT 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 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 rank	MANE	Protein	UniProt
FOXF2	NM_001452.2 link	c.121G>T	p.Ala41Ser	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1	Q12947

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2 link	c.121G>T	p.Ala41Ser	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1		Q12947
MIR6720	ENST00000611664.1 link	n.*246C>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

288

AN:

149642

Hom.:

Cov.:

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:

AN:

75792

Hom.:

AF XY:

0.00135

AC XY:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00195

ExAC

AF:

0.000372

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXF2-related disorder

Benign:1

Feb 15, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.26

.;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.34

N;N

PrimateAI

Pathogenic

0.84

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over