NM_014009.4:c.-23+2877C>A

Variant names:

• chrX-49261784-G-T
• rs3761548
• NM_014009.4:c.-23+2877C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 221 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

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.-23+2877C>A		intron	N/A	NP_054728.2
	FOXP3	NM_001114377.2		c.-23+2877C>A		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.-23+2877C>A		intron	N/A	ENSP00000365380.4	Q9BZS1-1
	ENSG00000290184	ENST00000703450.1		c.-22-3257C>A		intron	N/A	ENSP00000515301.1	A0A494C1K1
	FOXP3	ENST00000557224.6	TSL:2	c.-23+2877C>A		intron	N/A	ENSP00000451208.1	Q9BZS1-3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 35822 AN: 111122 Hom.: 5197 Cov.: 23

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

African (AFR) AF: 0.0930 AC: 2863 AN: 30785

American (AMR) AF: 0.284 AC: 3010 AN: 10595

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1291 AN: 2636

East Asian (EAS) AF: 0.182 AC: 635 AN: 3493

South Asian (SAS) AF: 0.296 AC: 780 AN: 2632

European-Finnish (FIN) AF: 0.374 AC: 2226 AN: 5958

Middle Eastern (MID) AF: 0.488 AC: 103 AN: 211

European-Non Finnish (NFE) AF: 0.456 AC: 24041 AN: 52679

Other (OTH) AF: 0.353 AC: 538 AN: 1522

Alfa AF: 0.290 Hom.: 4423

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs3761548; hg19: chrX-49118241;