rs2232366

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.210+87G>T		intron_variant		ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.210+87G>T		intron_variant			NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.210+87G>T		intron_variant		1	NM_014009.4	ENSP00000365380.4

Frequencies

GnomAD3 genomes AF: 0.000516 AC: 58 AN: 112481 Hom.: 0 Cov.: 24 AF XY: 0.000693 AC XY: 24 AN XY: 34625

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

Gnomad4 AFR exome AF: 0.0000594

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.000507

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000486

Gnomad4 OTH exome AF: 0.000483

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000929

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

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	14
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs2232366; hg19: chrX-49114666;