chr6-1390209-G-A

Variant names:

• chr6-1390209-G-A
• rs72667003
• NM_001452.2:c.262G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 7 publications found

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

LINC01394 (HGNC:50670): (long intergenic non-protein coding RNA 1394)

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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4132 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001452.2. 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
	FOXF2	NM_001452.2	MANE Select	c.262G>A	p.Ala88Thr	missense	Exon 1 of 2	NP_001443.1	Q12947
	FOXF2-DT	NR_189293.1		n.331C>T		non_coding_transcript_exon	Exon 1 of 3
	FOXF2-DT	NR_189294.1		n.68+783C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	ENST00000645481.2	MANE Select	c.262G>A	p.Ala88Thr	missense	Exon 1 of 2	ENSP00000496415.1	Q12947
	LINC01394	ENST00000721686.1		n.89+783C>T		intron	N/A
	LINC01394	ENST00000721687.1		n.68+783C>T		intron	N/A

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

GnomAD2 exomes AF: 0.0369 AC: 5711 AN: 154626 AF XY: 0.0371

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 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

African (AFR) AF: 0.0154 AC: 446 AN: 28940

American (AMR) AF: 0.0141 AC: 486 AN: 34364

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1244 AN: 24218

East Asian (EAS) AF: 0.0409 AC: 1421 AN: 34724

South Asian (SAS) AF: 0.0440 AC: 3394 AN: 77192

European-Finnish (FIN) AF: 0.0272 AC: 1257 AN: 46198

Middle Eastern (MID) AF: 0.0530 AC: 225 AN: 4248

European-Non Finnish (NFE) AF: 0.0318 AC: 34262 AN: 1078076

Other (OTH) AF: 0.0360 AC: 2054 AN: 57014

GnomAD4 genome AF: 0.0273 AC: 4132 AN: 151344 Hom.: 68 Cov.: 32 AF XY: 0.0274 AC XY: 2028 AN XY: 73968

African (AFR) AF: 0.0131 AC: 540 AN: 41288

American (AMR) AF: 0.0246 AC: 375 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 164 AN: 3454

East Asian (EAS) AF: 0.0466 AC: 234 AN: 5024

South Asian (SAS) AF: 0.0408 AC: 196 AN: 4802

European-Finnish (FIN) AF: 0.0247 AC: 260 AN: 10518

Middle Eastern (MID) AF: 0.0385 AC: 11 AN: 286

European-Non Finnish (NFE) AF: 0.0334 AC: 2263 AN: 67716

Other (OTH) AF: 0.0348 AC: 73 AN: 2096

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 v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.72
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.76	N
REVEL	Benign	0.24
Sift	Benign	0.61	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.012
ClinPred		0.0029	T
GERP RS		-5.2
Varity_R		0.027
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72667003; hg19: chr6-1390444; COSMIC: COSV107274492;