X-49264991-C-A

Variant names:

• chrX-49264991-C-A
• rs782180627
• ENST00000703450.1:c.-23+1144G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The ENST00000703450.1(ENSG00000290184):​c.-23+1144G>T 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000016 (0 hom. 0 hem.)
• Consequence: ENSG00000290184 ENST00000703450.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 0 publications found

Genes affected

ENSG00000290184 (HGNC:):

FLICR (HGNC:53589): (FOXP3 regulating long intergenic non-coding RNA)

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290184	ENST00000703450.1	c.-23+1144G>T		intron_variant	Intron 3 of 3			ENSP00000515301.1
FLICR	ENST00000651462.1	n.1655G>T		non_coding_transcript_exon_variant	Exon 3 of 3
FOXP3	ENST00000376199.7	c.-353G>T		upstream_gene_variant		2		ENSP00000365372.2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 609717 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 163401

African (AFR) AF: 0.00 AC: 0 AN: 11876

American (AMR) AF: 0.00 AC: 0 AN: 791

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3788

East Asian (EAS) AF: 0.00 AC: 0 AN: 2903

South Asian (SAS) AF: 0.00 AC: 0 AN: 11264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 261

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1024

European-Non Finnish (NFE) AF: 0.00000179 AC: 1 AN: 557654

Other (OTH) AF: 0.00 AC: 0 AN: 20156

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		3.3
PromoterAI		0.0019	Neutral

Splicing

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

Other links and lift over

dbSNP: rs782180627; hg19: chrX-49121453;