chr16-86510601-C-A

Variant names:

• chr16-86510601-C-A
• rs1047402909
• NM_001451.3:c.32C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001451.3(FOXF1):​c.32C>A​(p.Pro11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,387,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: FOXF1 NM_001451.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.295
• Publications: 0 publications found

Genes affected

FOXF1 (HGNC:3809): (forkhead box F1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

FOXF1 Gene-Disease associations (from GenCC):

• alveolar capillary dysplasia with misalignment of pulmonary veins

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29092228).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001451.3. 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
	FOXF1	NM_001451.3	MANE Select	c.32C>A	p.Pro11Gln	missense	Exon 1 of 2	NP_001442.2	Q12946

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.32C>A	p.Pro11Gln	missense	Exon 1 of 2	ENSP00000262426.4	Q12946

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151408 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000482

GnomAD4 exome AF: 0.0000315 AC: 39 AN: 1236214 Hom.: 0 Cov.: 33 AF XY: 0.0000397 AC XY: 24 AN XY: 604924

African (AFR) AF: 0.000126 AC: 3 AN: 23854

American (AMR) AF: 0.000166 AC: 2 AN: 12078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17372

East Asian (EAS) AF: 0.00 AC: 0 AN: 28700

South Asian (SAS) AF: 0.00 AC: 0 AN: 51310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3810

European-Non Finnish (NFE) AF: 0.0000316 AC: 32 AN: 1012314

Other (OTH) AF: 0.0000396 AC: 2 AN: 50512

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151408 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 73972

African (AFR) AF: 0.0000242 AC: 1 AN: 41252

American (AMR) AF: 0.000131 AC: 2 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67774

Other (OTH) AF: 0.000482 AC: 1 AN: 2076

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	FOXF1-related disorder (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	0.0	N
PhyloP100		0.29
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.29
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.30	T
Polyphen		0.96	D
Vest4		0.17
MutPred		0.22		Loss of glycosylation at P11 (P = 0.0564)
MVP		0.61
ClinPred		0.36	T
GERP RS		1.1
PromoterAI		0.028	Neutral
Varity_R		0.15
gMVP		0.53
Mutation Taster		=69/31	polymorphism

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: rs1047402909; hg19: chr16-86544207;