X-49258209-C-T

Variant names:

• chrX-49258209-C-T
• rs2232366
• NM_014009.4:c.210+87G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014009.4(FOXP3):​c.210+87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 671,645 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 24)
  • Exomes 𝑓: 0.0000015 (0 hom. 1 hem.)
• Consequence: FOXP3 NM_014009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 3 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ENSG00000290184 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014009.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP3	NM_014009.4	MANE Select	c.210+87G>A		intron	N/A	NP_054728.2
	FOXP3	NM_001114377.2		c.210+87G>A		intron	N/A	NP_001107849.1	Q9BZS1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP3	ENST00000376207.10	TSL:1 MANE Select	c.210+87G>A		intron	N/A	ENSP00000365380.4	Q9BZS1-1
	FOXP3	ENST00000518685.6	TSL:1	c.210+87G>A		intron	N/A	ENSP00000428952.2	Q9BZS1-4
	FOXP3	ENST00000557224.6	TSL:2	c.210+87G>A		intron	N/A	ENSP00000451208.1	Q9BZS1-3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000149 AC: 1 AN: 671645 Hom.: 0 AF XY: 0.00000566 AC XY: 1 AN XY: 176637

African (AFR) AF: 0.00 AC: 0 AN: 16822

American (AMR) AF: 0.00 AC: 0 AN: 19210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13412

East Asian (EAS) AF: 0.00 AC: 0 AN: 24919

South Asian (SAS) AF: 0.0000282 AC: 1 AN: 35488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2275

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 493802

Other (OTH) AF: 0.00 AC: 0 AN: 31065

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		2.1
PromoterAI		-0.072	Neutral

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: rs2232366; hg19: chrX-49114666;