rs1161631447

Variant names:

• chr16-86510607-G-T
• rs1161631447
• NM_001451.3:c.38G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001451.3(FOXF1):​c.38G>T​(p.Gly13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000325 in 1,229,436 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FOXF1 NM_001451.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.832
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16219258).

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.38G>T	p.Gly13Val	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.38G>T	p.Gly13Val	missense	Exon 1 of 2	ENSP00000262426.4	Q12946

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150740 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18560 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 3 AN: 1078696 Hom.: 0 Cov.: 34 AF XY: 0.00000385 AC XY: 2 AN XY: 519368

African (AFR) AF: 0.00 AC: 0 AN: 21326

American (AMR) AF: 0.00 AC: 0 AN: 8252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13490

East Asian (EAS) AF: 0.00 AC: 0 AN: 23104

South Asian (SAS) AF: 0.00 AC: 0 AN: 31928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3256

European-Non Finnish (NFE) AF: 0.00000330 AC: 3 AN: 909252

Other (OTH) AF: 0.00 AC: 0 AN: 42470

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150740 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73592

African (AFR) AF: 0.00 AC: 0 AN: 41226

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67532

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.035	D
MutationAssessor	Benign	0.0	N
PhyloP100		0.83
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.17	T
Polyphen		0.18	B
Vest4		0.23
MutPred		0.24		Loss of relative solvent accessibility (P = 0.0981)
MVP		0.43
ClinPred		0.28	T
GERP RS		2.5
PromoterAI		-0.014	Neutral
Varity_R		0.17
gMVP		0.44
Mutation Taster		=86/14	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: rs1161631447; hg19: chr16-86544213;