rs2280883

Variant names:

• chrX-49252667-T-C
• rs2280883
• NM_014009.4:c.1044+459A>G

Variant summary

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

The NM_014009.4(FOXP3):​c.1044+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.31 (4669 hom., 8961 hem., cov: 20)
• Consequence: FOXP3 NM_014009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 57 publications found

Genes affected

FOXP3 (HGNC:6106): (forkhead box P3) The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FOXP3 Gene-Disease associations (from GenCC):

• immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.1044+459A>G		intron_variant	Intron 10 of 11	ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.939+459A>G		intron_variant	Intron 9 of 10		NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.1044+459A>G		intron_variant	Intron 10 of 11	1	NM_014009.4	ENSP00000365380.4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 33004 AN: 107981 Hom.: 4673 Cov.: 20

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 32998 AN: 108037 Hom.: 4669 Cov.: 20 AF XY: 0.294 AC XY: 8961 AN XY: 30503

African (AFR) AF: 0.0732 AC: 2179 AN: 29759

American (AMR) AF: 0.265 AC: 2653 AN: 10024

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1149 AN: 2603

East Asian (EAS) AF: 0.190 AC: 647 AN: 3404

South Asian (SAS) AF: 0.297 AC: 723 AN: 2434

European-Finnish (FIN) AF: 0.371 AC: 2022 AN: 5452

Middle Eastern (MID) AF: 0.467 AC: 98 AN: 210

European-Non Finnish (NFE) AF: 0.437 AC: 22720 AN: 52020

Other (OTH) AF: 0.332 AC: 489 AN: 1471

Alfa AF: 0.388 Hom.: 37220

Bravo AF: 0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.77
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280883; hg19: chrX-49109128;