6-1390041-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

• chr6-1390041-C-CCCG
• rs747033801
• NM_001452.2:c.121_123dupGCC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001452.2(FOXF2):​c.121_123dupGCC​(p.Ala41dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 1,354,102 control chromosomes in the GnomAD database, including 155 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P42P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.020 (39 hom., cov: 31)
  • Exomes 𝑓: 0.017 (116 hom.)
• Consequence: FOXF2 NM_001452.2 conservative_inframe_insertion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.89
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 6-1390041-C-CCCG is Benign according to our data. Variant chr6-1390041-C-CCCG is described in ClinVar as Benign. ClinVar VariationId is 3055662.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

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.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2	NP_001443.1	Q12947
	FOXF2-DT	NR_189293.1		n.458+38_458+40dupCGG		intron	N/A
	FOXF2-DT	NR_189294.1		n.69-818_69-816dupCGG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	ENST00000645481.2	MANE Select	c.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2	ENSP00000496415.1	Q12947
	LINC01394	ENST00000721686.1		n.89+948_89+950dupCGG		intron	N/A
	LINC01394	ENST00000721687.1		n.69-818_69-816dupCGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2865 AN: 145186 Hom.: 39 Cov.: 31

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00225

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0236

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0164

GnomAD2 exomes AF: 0.0318 AC: 1084 AN: 34036 AF XY: 0.0310

Gnomad AFR exome AF: 0.0288

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.0273

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.0640

Gnomad NFE exome AF: 0.0274

Gnomad OTH exome AF: 0.0303

GnomAD4 exome AF: 0.0174 AC: 21024 AN: 1208818 Hom.: 116 Cov.: 28 AF XY: 0.0176 AC XY: 10452 AN XY: 593484

African (AFR) AF: 0.0117 AC: 284 AN: 24344

American (AMR) AF: 0.0132 AC: 285 AN: 21532

Ashkenazi Jewish (ASJ) AF: 0.0131 AC: 253 AN: 19260

East Asian (EAS) AF: 0.126 AC: 2885 AN: 22958

South Asian (SAS) AF: 0.0129 AC: 759 AN: 58824

European-Finnish (FIN) AF: 0.0329 AC: 926 AN: 28124

Middle Eastern (MID) AF: 0.0126 AC: 43 AN: 3424

European-Non Finnish (NFE) AF: 0.0151 AC: 14785 AN: 982126

Other (OTH) AF: 0.0167 AC: 804 AN: 48226

GnomAD4 genome AF: 0.0197 AC: 2864 AN: 145284 Hom.: 39 Cov.: 31 AF XY: 0.0206 AC XY: 1459 AN XY: 70760

African (AFR) AF: 0.0132 AC: 529 AN: 40200

American (AMR) AF: 0.0115 AC: 169 AN: 14708

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 52 AN: 3390

East Asian (EAS) AF: 0.0894 AC: 432 AN: 4832

South Asian (SAS) AF: 0.0194 AC: 91 AN: 4692

European-Finnish (FIN) AF: 0.0403 AC: 344 AN: 8540

Middle Eastern (MID) AF: 0.0217 AC: 6 AN: 276

European-Non Finnish (NFE) AF: 0.0184 AC: 1207 AN: 65730

Other (OTH) AF: 0.0158 AC: 32 AN: 2026

Alfa AF: 0.00452 Hom.: 2

ClinVar

ClinVar submissions

Significance: 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		1.9
Mutation Taster		=85/15	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; COSMIC: COSV52526519; COSMIC: COSV52526519;