rs72667003

chr6-1390209-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. 13/18 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 4125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXF2	NM_001452.2	c.262G>A	p.Ala88Thr	missense_variant	1/2	ENST00000645481.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXF2	ENST00000645481.2	c.262G>A	p.Ala88Thr	missense_variant	1/2		NM_001452.2	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4125 AN: 151234 Hom.: 68 Cov.: 32

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

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.: 31 AF XY: 0.0327 AC XY: 22421 AN XY: 685900

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.: 68 Cov.: 32 AF XY: 0.0274 AC XY: 2028 AN XY: 73968

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.: 37

Bravo AF: 0.0267

TwinsUK AF: 0.0256 AC: 95

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.0131 AC: 53

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	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	11
Dann	Benign	0.95
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.085	N
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.83	D
Polyphen		0.0	B;B
Vest4		0.012
ClinPred		0.0029	T
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

Other links and lift over

dbSNP: rs72667003; hg19: chr6-1390444;