X-49261784-G-T

Position:

• chrX-49261784-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014009.4(FOXP3):​c.-23+2877C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 111,175 control chromosomes in the GnomAD database, including 5,192 homozygotes. There are 10,261 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 0.32 (5192 hom., 10261 hem., cov: 23)
• Consequence: FOXP3 NM_014009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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]

ENSG00000290184 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.-23+2877C>A		intron_variant		ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.-23+2877C>A		intron_variant			NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.-23+2877C>A		intron_variant		1	NM_014009.4	ENSP00000365380.4
ENSG00000290184	ENST00000703450.1	c.-22-3257C>A		intron_variant				ENSP00000515301.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 35822 AN: 111122 Hom.: 5197 Cov.: 23 AF XY: 0.308 AC XY: 10249 AN XY: 33310

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.322 AC: 35811 AN: 111175 Hom.: 5192 Cov.: 23 AF XY: 0.307 AC XY: 10261 AN XY: 33373

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.353

Alfa AF: 0.249 Hom.: 1612

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3761548; hg19: chrX-49118241;