16-86510604-ACGG-A

Position:

• chr16-86510604-ACGG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001451.3(FOXF1):​c.57_59del​(p.Gly23del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,181,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXF1 NM_001451.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-86510604-ACGG-A is Benign according to our data. Variant chr16-86510604-ACGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646946.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-86510604-ACGG-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00341 (4025/1181552) while in subpopulation SAS AF= 0.0193 (898/46522). AF 95% confidence interval is 0.0183. There are 0 homozygotes in gnomad4_exome. There are 2391 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 4025 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXF1	NM_001451.3	c.57_59del	p.Gly23del	inframe_deletion	1/2	ENST00000262426.6	NP_001442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXF1	ENST00000262426.6	c.57_59del	p.Gly23del	inframe_deletion	1/2	1	NM_001451.3	ENSP00000262426	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 150132 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.000579

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.0251 AC: 556 AN: 22192 Hom.: 0 AF XY: 0.0252 AC XY: 333 AN XY: 13220

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.0462

Gnomad ASJ exome AF: 0.0143

Gnomad EAS exome AF: 0.0623

Gnomad SAS exome AF: 0.0219

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0343

GnomAD4 exome AF: 0.00341 AC: 4025 AN: 1181552 Hom.: 0 AF XY: 0.00415 AC XY: 2391 AN XY: 575520

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00983

Gnomad4 ASJ exome AF: 0.00454

Gnomad4 EAS exome AF: 0.00302

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.00891

Gnomad4 NFE exome AF: 0.00241

Gnomad4 OTH exome AF: 0.00370

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000666 AC: 10 AN: 150132 Hom.: 0 Cov.: 32 AF XY: 0.0000682 AC XY: 5 AN XY: 73276

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.000579

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000295

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.000484

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

FOXF1: PM4:Supporting, BS1 -

Computational scores

Source: dbNSFP v4.3

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: rs574179816; hg19: chr16-86544210;