Genetic Variant FOXP3:c.-22-902A>G (chrX-49259429-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014009.4(FOXP3):c.-22-902A>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 0.62 ( 15614 hom., 18214 hem., cov: 21)

Failed GnomAD Quality Control

Consequence

FOXP3
NM_014009.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.68

Publications

112 publications found

Variant links:

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: G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

FOXP3 links:

ENSG00000290184 (HGNC:):

ENSG00000290184 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014009.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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.-22-902A>G		intron	N/A	NP_054728.2
	FOXP3	NM_001114377.2		c.-22-902A>G		intron	N/A	NP_001107849.1	Q9BZS1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOXP3	ENST00000376207.10	TSL:1 MANE Select	c.-22-902A>G	intron	N/A	ENSP00000365380.4	Q9BZS1-1
ENSG00000290184	ENST00000703450.1		c.-22-902A>G	intron	N/A	ENSP00000515301.1	A0A494C1K1
FOXP3	ENST00000557224.6	TSL:2	c.-22-902A>G	intron	N/A	ENSP00000451208.1	Q9BZS1-3

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

66596

AN:

108210

Hom.:

15616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.781

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.584

Gnomad OTH

AF:

0.582

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

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.616

AC:

66656

AN:

108266

Hom.:

15614

Cov.:

AF XY:

0.593

AC XY:

18214

AN XY:

30696

show subpopulations

African (AFR)

AF:

0.781

AC:

23106

AN:

29601

American (AMR)

AF:

0.477

AC:

4873

AN:

10213

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

1522

AN:

2609

East Asian (EAS)

AF:

0.381

AC:

1299

AN:

3408

South Asian (SAS)

AF:

0.575

AC:

1401

AN:

2435

European-Finnish (FIN)

AF:

0.486

AC:

2687

AN:

5526

Middle Eastern (MID)

AF:

0.608

AC:

129

AN:

212

European-Non Finnish (NFE)

AF:

0.584

AC:

30416

AN:

52116

Other (OTH)

AF:

0.585

AC:

874

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

890

1780

2671

3561

4451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.613

Hom.:

11563

Bravo

AF:

0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0040

(source)

DANN

Benign

0.28

PhyloP100

-5.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over