X-49264716-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 435253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 100 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000703450.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP3	NM_014009.4	MANE Select	c.-78C>T		upstream_gene	N/A	NP_054728.2
	FOXP3	NM_001114377.2		c.-78C>T		upstream_gene	N/A	NP_001107849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290184	ENST00000703450.1		c.-23+1419C>T		intron	N/A	ENSP00000515301.1
	FOXP3	ENST00000376199.7	TSL:2	c.-78C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000365372.2
	FLICR	ENST00000651462.1		n.1930C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 331 AN: 110598 Hom.: 0 Cov.: 22

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

African (AFR) AF: 0.000242 AC: 3 AN: 12407

American (AMR) AF: 0.00122 AC: 1 AN: 819

Ashkenazi Jewish (ASJ) AF: 0.00478 AC: 19 AN: 3972

East Asian (EAS) AF: 0.000331 AC: 1 AN: 3020

South Asian (SAS) AF: 0.000417 AC: 5 AN: 11994

European-Finnish (FIN) AF: 0.00181 AC: 1 AN: 552

Middle Eastern (MID) AF: 0.000905 AC: 1 AN: 1105

European-Non Finnish (NFE) AF: 0.00589 AC: 3449 AN: 585763

Other (OTH) AF: 0.00345 AC: 73 AN: 21167

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

African (AFR) AF: 0.000559 AC: 17 AN: 30422

American (AMR) AF: 0.00124 AC: 13 AN: 10460

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 10 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3505

South Asian (SAS) AF: 0.00 AC: 0 AN: 2569

European-Finnish (FIN) AF: 0.00327 AC: 19 AN: 5813

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00488 AC: 258 AN: 52851

Other (OTH) AF: 0.00134 AC: 2 AN: 1490

Alfa AF: 0.00292 Hom.: 18

Bravo AF: 0.00296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.1
PromoterAI		-0.056	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs141704699; hg19: chrX-49121178;