chr6-1390041-C-CCCG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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).

• 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

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]

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

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2	ENST00000645481.2	NP_001443.1
FOXF2-DT	NR_189293.1	n.458+38_458+40dupCGG		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1	n.69-818_69-816dupCGG		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1	n.68+948_68+950dupCGG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.121_123dupGCC	p.Ala41dup	conservative_inframe_insertion	Exon 1 of 2		NM_001452.2	ENSP00000496415.1

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

GnomAD3 exomes AF: 0.0318 AC: 1084 AN: 34036 Hom.: 1 AF XY: 0.0310 AC XY: 613 AN XY: 19760

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 SAS exome AF: 0.0281

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

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0167

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

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0894

Gnomad4 SAS AF: 0.0194

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FOXF2-related disorder Benign:1

Sep 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs747033801; hg19: chr6-1390276;