rs72667003

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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	Appris	UniProt
FOXF2	ENST00000645481.2 link	c.262G>A	p.Ala88Thr	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1		Q12947
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

GnomAD3 exomes

AF:

0.0369

AC:

5711

AN:

154626

Hom.:

177

AF XY:

0.0371

AC XY:

3206

AN XY:

86462

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 SAS exome

AF:

0.0504

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

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0514

Gnomad4 EAS exome

AF:

0.0409

Gnomad4 SAS exome

AF:

0.0440

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0273

AC:

4132

AN:

151344

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2028

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0475

Gnomad4 EAS

AF:

0.0466

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0247

Gnomad4 NFE

AF:

0.0334

Gnomad4 OTH

AF:

0.0348

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over