X-49264716-G-A

Variant names:

• chrX-49264716-G-A
• rs141704699
• ENST00000703450.1:c.-23+1419C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000703450.1(ENSG00000290184):​c.-23+1419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 751,444 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,146 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., 100 hem., cov: 22)
  • Exomes 𝑓: 0.0055 (7 hom. 1046 hem.)
• Consequence: ENSG00000290184 ENST00000703450.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

Genes affected

ENSG00000290184 (HGNC:):

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]

ENSG00000286181 (HGNC:53589): (FOXP3 regulating long intergenic non-coding RNA)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant X-49264716-G-A is Benign according to our data. Variant chrX-49264716-G-A is described in ClinVar as [Benign]. Clinvar id is 435253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 100 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.-78C>T		upstream_gene_variant		ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.-78C>T		upstream_gene_variant			NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290184	ENST00000703450.1	c.-23+1419C>T		intron_variant	Intron 3 of 3			ENSP00000515301.1
FOXP3	ENST00000376207.10	c.-78C>T		upstream_gene_variant		1	NM_014009.4	ENSP00000365380.4

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 331 AN: 110598 Hom.: 0 Cov.: 22 AF XY: 0.00305 AC XY: 100 AN XY: 32832

Gnomad AFR AF: 0.000560

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00136

GnomAD4 exome AF: 0.00554 AC: 3553 AN: 640799 Hom.: 7 Cov.: 27 AF XY: 0.00544 AC XY: 1046 AN XY: 192233

Gnomad4 AFR exome AF: 0.000242

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.000331

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00181

Gnomad4 NFE exome AF: 0.00589

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00299 AC: 331 AN: 110645 Hom.: 0 Cov.: 22 AF XY: 0.00304 AC XY: 100 AN XY: 32891

Gnomad4 AFR AF: 0.000559

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00379

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00327

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00134

Alfa AF: 0.00292 Hom.: 18

Bravo AF: 0.00296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 01, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141704699; hg19: chrX-49121178;