6-1394808-T-C

Variant names:

• chr6-1394808-T-C
• rs2293783
• NM_001452.2:c.1284T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001452.2(FOXF2):​c.1284T>C​(p.Tyr428Tyr) 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
• Publications: 20 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	NM_001452.2	MANE Select	c.1284T>C	p.Tyr428Tyr	synonymous	Exon 2 of 2	NP_001443.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF2	ENST00000645481.2	MANE Select	c.1284T>C	p.Tyr428Tyr	synonymous	Exon 2 of 2	ENSP00000496415.1

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

GnomAD2 exomes AF: 0.215 AC: 54063 AN: 251486 AF XY: 0.219

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 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

African (AFR) AF: 0.153 AC: 5125 AN: 33474

American (AMR) AF: 0.228 AC: 10190 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6933 AN: 26134

East Asian (EAS) AF: 0.260 AC: 10323 AN: 39694

South Asian (SAS) AF: 0.213 AC: 18411 AN: 86256

European-Finnish (FIN) AF: 0.157 AC: 8402 AN: 53414

Middle Eastern (MID) AF: 0.349 AC: 2015 AN: 5768

European-Non Finnish (NFE) AF: 0.215 AC: 238748 AN: 1111704

Other (OTH) AF: 0.220 AC: 13264 AN: 60390

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

African (AFR) AF: 0.156 AC: 6463 AN: 41494

American (AMR) AF: 0.216 AC: 3304 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4818

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10580

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14983 AN: 67994

Other (OTH) AF: 0.257 AC: 542 AN: 2110

Alfa AF: 0.220 Hom.: 15776

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Benign	0.43
PhyloP100		0.36
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293783; hg19: chr6-1395043; COSMIC: COSV52525078; COSMIC: COSV52525078;