16-86513749-A-G

Variant names:

• chr16-86513749-A-G
• rs1064259
• NM_001451.3:c.*664A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001451.3(FOXF1):​c.*664A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,266 control chromosomes in the GnomAD database, including 50,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50393 hom., cov: 33)
  • Exomes 𝑓: 0.69 (20 hom.)
• Consequence: FOXF1 NM_001451.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	NM_001451.3	MANE Select	c.*664A>G		3_prime_UTR	Exon 2 of 2	NP_001442.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.*664A>G		3_prime_UTR	Exon 2 of 2	ENSP00000262426.4

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123488 AN: 152074 Hom.: 50338 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.689 AC: 51 AN: 74 Hom.: 20 Cov.: 0 AF XY: 0.682 AC XY: 30 AN XY: 44

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.688 AC: 44 AN: 64

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.812 AC: 123603 AN: 152192 Hom.: 50393 Cov.: 33 AF XY: 0.813 AC XY: 60457 AN XY: 74396

African (AFR) AF: 0.871 AC: 36182 AN: 41544

American (AMR) AF: 0.857 AC: 13118 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2814 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4564 AN: 5168

South Asian (SAS) AF: 0.696 AC: 3356 AN: 4824

European-Finnish (FIN) AF: 0.814 AC: 8606 AN: 10574

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52345 AN: 67990

Other (OTH) AF: 0.807 AC: 1707 AN: 2116

Alfa AF: 0.789 Hom.: 75150

Bravo AF: 0.823

Asia WGS AF: 0.784 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.59
PhyloP100		-0.010
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: rs1064259; hg19: chr16-86547355;