rs2232366

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-49258209-C-A
• chrX-49258209-C-G
• chrX-49258209-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014009.4(FOXP3):​c.210+87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 784,177 control chromosomes in the GnomAD database, including 6 homozygotes. There are 199 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: 𝑓 0.00050 (0 hom., 23 hem., cov: 24)
  • Exomes 𝑓: 0.00087 (6 hom. 176 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000498 (56/112535) while in subpopulation EAS AF = 0.0141 (50/3552). AF 95% confidence interval is 0.011. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 23 XL gene

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>T		intron	N/A	NP_054728.2
	FOXP3	NM_001114377.2		c.210+87G>T		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>T		intron	N/A	ENSP00000365380.4	Q9BZS1-1
	FOXP3	ENST00000518685.6	TSL:1	c.210+87G>T		intron	N/A	ENSP00000428952.2	Q9BZS1-4
	FOXP3	ENST00000557224.6	TSL:2	c.210+87G>T		intron	N/A	ENSP00000451208.1	Q9BZS1-3

Frequencies

GnomAD3 genomes AF: 0.000516 AC: 58 AN: 112481 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000930

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000871 AC: 585 AN: 671642 Hom.: 6 AF XY: 0.000996 AC XY: 176 AN XY: 176636

African (AFR) AF: 0.0000594 AC: 1 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: 0.0211 AC: 526 AN: 24916

South Asian (SAS) AF: 0.000507 AC: 18 AN: 35488

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

Middle Eastern (MID) AF: 0.000440 AC: 1 AN: 2275

European-Non Finnish (NFE) AF: 0.0000486 AC: 24 AN: 493802

Other (OTH) AF: 0.000483 AC: 15 AN: 31065

GnomAD4 genome AF: 0.000498 AC: 56 AN: 112535 Hom.: 0 Cov.: 24 AF XY: 0.000663 AC XY: 23 AN XY: 34689

African (AFR) AF: 0.00 AC: 0 AN: 30985

American (AMR) AF: 0.0000929 AC: 1 AN: 10761

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.0141 AC: 50 AN: 3552

South Asian (SAS) AF: 0.00146 AC: 4 AN: 2735

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6211

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53200

Other (OTH) AF: 0.00 AC: 0 AN: 1530

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		2.1
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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;