6-1390041-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCG

Variant names:

• chr6-1390041-CCCGCCGCCG-C
• rs747033801
• NM_001452.2:c.115_123delGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001452.2(FOXF2):​c.115_123delGCCGCCGCC​(p.Ala39_Ala41del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,354,610 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: FOXF2 NM_001452.2 conservative_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.31
• Publications: 0 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]

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

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

ACMG classification

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

• BP6: Variant 6-1390041-CCCGCCGCCG-C is Benign according to our data. Variant chr6-1390041-CCCGCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3041547.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 245 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.115_123delGCCGCCGCC	p.Ala39_Ala41del	conservative_inframe_deletion	Exon 1 of 2	NP_001443.1	Q12947
	FOXF2-DT	NR_189293.1		n.458+32_458+40delCGGCGGCGG		intron	N/A
	FOXF2-DT	NR_189294.1		n.69-824_69-816delCGGCGGCGG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	ENST00000645481.2	MANE Select	c.115_123delGCCGCCGCC	p.Ala39_Ala41del	conservative_inframe_deletion	Exon 1 of 2	ENSP00000496415.1	Q12947
	LINC01394	ENST00000721686.1		n.89+942_89+950delCGGCGGCGG		intron	N/A
	LINC01394	ENST00000721687.1		n.69-824_69-816delCGGCGGCGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 245 AN: 145194 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00136

Gnomad ASJ AF: 0.00206

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000468

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000502

Gnomad OTH AF: 0.00249

GnomAD2 exomes AF: 0.00167 AC: 57 AN: 34036 AF XY: 0.00147

Gnomad AFR exome AF: 0.00962

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00138

Gnomad EAS exome AF: 0.00221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.000686 AC: 830 AN: 1209318 Hom.: 1 AF XY: 0.000677 AC XY: 402 AN XY: 593744

African (AFR) AF: 0.00439 AC: 107 AN: 24354

American (AMR) AF: 0.00167 AC: 36 AN: 21576

Ashkenazi Jewish (ASJ) AF: 0.000778 AC: 15 AN: 19282

East Asian (EAS) AF: 0.000347 AC: 8 AN: 23046

South Asian (SAS) AF: 0.000798 AC: 47 AN: 58872

European-Finnish (FIN) AF: 0.0000355 AC: 1 AN: 28164

Middle Eastern (MID) AF: 0.00292 AC: 10 AN: 3422

European-Non Finnish (NFE) AF: 0.000570 AC: 560 AN: 982360

Other (OTH) AF: 0.000954 AC: 46 AN: 48242

GnomAD4 genome AF: 0.00169 AC: 245 AN: 145292 Hom.: 1 Cov.: 31 AF XY: 0.00160 AC XY: 113 AN XY: 70768

African (AFR) AF: 0.00423 AC: 170 AN: 40202

American (AMR) AF: 0.00136 AC: 20 AN: 14708

Ashkenazi Jewish (ASJ) AF: 0.00206 AC: 7 AN: 3392

East Asian (EAS) AF: 0.00103 AC: 5 AN: 4832

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4692

European-Finnish (FIN) AF: 0.000468 AC: 4 AN: 8544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000502 AC: 33 AN: 65730

Other (OTH) AF: 0.00247 AC: 5 AN: 2026

Alfa AF: 0.00 Hom.: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FOXF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=195/5	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747033801; hg19: chr6-1390276;