6-1394808-T-C

Position:

• chr6-1394808-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001452.2(FOXF2):​c.1284T>C​(p.Tyr428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,680 control chromosomes in the GnomAD database, including 37,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3234 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34231 hom.)
• Consequence: FOXF2 NM_001452.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXF2	NM_001452.2	c.1284T>C	p.Tyr428=	synonymous_variant	2/2	ENST00000645481.2	NP_001443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2	c.1284T>C	p.Tyr428=	synonymous_variant	2/2		NM_001452.2	ENSP00000496415	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30402 AN: 152004 Hom.: 3229 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.215 AC: 54063 AN: 251486 Hom.: 5987 AF XY: 0.219 AC XY: 29726 AN XY: 135916

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.265

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.214 AC: 313411 AN: 1461558 Hom.: 34231 Cov.: 34 AF XY: 0.216 AC XY: 157096 AN XY: 727102

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.200 AC: 30429 AN: 152122 Hom.: 3234 Cov.: 32 AF XY: 0.197 AC XY: 14650 AN XY: 74358

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.257

Alfa AF: 0.224 Hom.: 7929

Bravo AF: 0.206

Asia WGS AF: 0.262 AC: 913 AN: 3478

EpiCase AF: 0.234

EpiControl AF: 0.243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2293783; hg19: chr6-1395043; COSMIC: COSV52525078; COSMIC: COSV52525078;