dbSNP rs2232366: FOXP3:c.210+87G>T (chrX-49258209-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

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

FOXP3 links:

ENSG00000290184 (HGNC:):

ENSG00000290184 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4 link	c.210+87G>T		intron_variant	Intron 2 of 11	ENST00000376207.10	NP_054728.2	Q9BZS1-1
FOXP3	NM_001114377.2 link	c.210+87G>T		intron_variant	Intron 2 of 10		NP_001107849.1	Q9BZS1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10 link	c.210+87G>T		intron_variant	Intron 2 of 11	1	NM_014009.4	ENSP00000365380.4		Q9BZS1-1
ENSG00000290184	ENST00000703450.1 link	c.*134G>T		downstream_gene_variant				ENSP00000515301.1		A0A494C1K1

Frequencies

GnomAD3 genomes

AF:

0.000516

AC:

AN:

112481

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000996

AC XY:

176

AN XY:

176636

show subpopulations

African (AFR)

AF:

0.0000594

AC:

AN:

16822

American (AMR)

AF:

0.00

AC:

AN:

19210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13412

East Asian (EAS)

AF:

0.0211

AC:

526

AN:

24916

South Asian (SAS)

AF:

0.000507

AC:

AN:

35488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34652

Middle Eastern (MID)

AF:

0.000440

AC:

AN:

2275

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

493802

Other (OTH)

AF:

0.000483

AC:

AN:

31065

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000498

AC:

AN:

112535

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

34689

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30985

American (AMR)

AF:

0.0000929

AC:

AN:

10761

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.0141

AC:

AN:

3552

South Asian (SAS)

AF:

0.00146

AC:

AN:

2735

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6211

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53200

Other (OTH)

AF:

0.00

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.1

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over