6-1390041-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCG

Variant names:

• chr6-1390041-CCCGCCGCCGCCG-C
• rs747033801
• NM_001452.2:c.112_123delGCCGCCGCCGCC

Variant summary

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

The NM_001452.2(FOXF2):​c.112_123delGCCGCCGCCGCC​(p.Ala38_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 0.000935 in 1,354,762 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00094 (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-CCCGCCGCCGCCG-C is Benign according to our data. Variant chr6-1390041-CCCGCCGCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3047212.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 125 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.112_123delGCCGCCGCCGCC	p.Ala38_Ala41del	conservative_inframe_deletion	Exon 1 of 2	NP_001443.1	Q12947
	FOXF2-DT	NR_189293.1		n.458+29_458+40delCGGCGGCGGCGG		intron	N/A
	FOXF2-DT	NR_189294.1		n.69-827_69-816delCGGCGGCGGCGG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	ENST00000645481.2	MANE Select	c.112_123delGCCGCCGCCGCC	p.Ala38_Ala41del	conservative_inframe_deletion	Exon 1 of 2	ENSP00000496415.1	Q12947
	LINC01394	ENST00000721686.1		n.89+939_89+950delCGGCGGCGGCGG		intron	N/A
	LINC01394	ENST00000721687.1		n.69-827_69-816delCGGCGGCGGCGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 125 AN: 145198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

Gnomad ASJ AF: 0.000590

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000852

Gnomad FIN AF: 0.000819

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00209 AC: 71 AN: 34036 AF XY: 0.00152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000915

Gnomad ASJ exome AF: 0.00381

Gnomad EAS exome AF: 0.00221

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.00342

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.000944 AC: 1142 AN: 1209466 Hom.: 1 AF XY: 0.000914 AC XY: 543 AN XY: 593834

African (AFR) AF: 0.000123 AC: 3 AN: 24356

American (AMR) AF: 0.000278 AC: 6 AN: 21578

Ashkenazi Jewish (ASJ) AF: 0.00197 AC: 38 AN: 19284

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

South Asian (SAS) AF: 0.000374 AC: 22 AN: 58888

European-Finnish (FIN) AF: 0.00110 AC: 31 AN: 28174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3424

European-Non Finnish (NFE) AF: 0.00102 AC: 1002 AN: 982468

Other (OTH) AF: 0.000663 AC: 32 AN: 48248

GnomAD4 genome AF: 0.000860 AC: 125 AN: 145296 Hom.: 0 Cov.: 31 AF XY: 0.000918 AC XY: 65 AN XY: 70768

African (AFR) AF: 0.000323 AC: 13 AN: 40206

American (AMR) AF: 0.0000680 AC: 1 AN: 14706

Ashkenazi Jewish (ASJ) AF: 0.000590 AC: 2 AN: 3392

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

South Asian (SAS) AF: 0.000853 AC: 4 AN: 4692

European-Finnish (FIN) AF: 0.000819 AC: 7 AN: 8544

Middle Eastern (MID) AF: 0.00362 AC: 1 AN: 276

European-Non Finnish (NFE) AF: 0.00140 AC: 92 AN: 65732

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.00123 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		=194/6	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;