6-1390041-CCCG-C

Position:

• chr6-1390041-CCCG-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001452.2(FOXF2):​c.121_123del​(p.Ala41del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,247,212 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.022 (1 hom.)
• Consequence: FOXF2 NM_001452.2 inframe_deletion
• 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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 6-1390041-CCCG-C is Benign according to our data. Variant chr6-1390041-CCCG-C is described in ClinVar as [Benign]. Clinvar id is 3055285.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.121_123del	p.Ala41del	inframe_deletion	1/2	ENST00000645481.2	NP_001443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.121_123del	p.Ala41del	inframe_deletion	1/2		NM_001452.2	ENSP00000496415	P1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 179 AN: 145168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000350

Gnomad OTH AF: 0.000499

GnomAD3 exomes AF: 0.0667 AC: 2269 AN: 34036 Hom.: 0 AF XY: 0.0660 AC XY: 1304 AN XY: 19760

Gnomad AFR exome AF: 0.0457

Gnomad AMR exome AF: 0.0721

Gnomad ASJ exome AF: 0.0713

Gnomad EAS exome AF: 0.0940

Gnomad SAS exome AF: 0.0683

Gnomad FIN exome AF: 0.0520

Gnomad NFE exome AF: 0.0637

Gnomad OTH exome AF: 0.0649

GnomAD4 exome AF: 0.0222 AC: 24507 AN: 1101948 Hom.: 1 AF XY: 0.0236 AC XY: 12580 AN XY: 533458

Gnomad4 AFR exome AF: 0.0239

Gnomad4 AMR exome AF: 0.0486

Gnomad4 ASJ exome AF: 0.0327

Gnomad4 EAS exome AF: 0.0197

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0251

GnomAD4 genome AF: 0.00127 AC: 184 AN: 145264 Hom.: 0 Cov.: 31 AF XY: 0.00129 AC XY: 91 AN XY: 70750

Gnomad4 AFR AF: 0.00333

Gnomad4 AMR AF: 0.00109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.000350

Gnomad4 OTH AF: 0.000494

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FOXF2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2019

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

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: rs747033801; hg19: chr6-1390276;