Genetic Variant ENSG00000290184:c.-23+1144G>C (chrX-49264991-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000703450.1(ENSG00000290184):c.-23+1144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 7 hem., cov: 20)

Exomes 𝑓: 0.00021 ( 0 hom. 39 hem. )

Consequence

ENSG00000290184
ENST00000703450.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Publications

0 publications found

Variant links:

Genes affected

ENSG00000290184 (HGNC:):

ENSG00000290184 links:

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

FLICR links:

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

FOXP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000290184	ENST00000703450.1 link	c.-23+1144G>C	intron_variant	Intron 3 of 3		ENSP00000515301.1	A0A494C1K1
FLICR	ENST00000651462.1 link	n.1655G>C	non_coding_transcript_exon_variant	Exon 3 of 3
FOXP3	ENST00000376199.7 link	c.-353G>C	upstream_gene_variant		2	ENSP00000365372.2	Q9BZS1-2

Frequencies

GnomAD3 genomes

AF:

0.000294

AC:

AN:

105561

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000698

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000103

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000232

Gnomad OTH

AF:

0.000709

GnomAD4 exome

AF:

0.000205

AC:

125

AN:

609717

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

163401

show subpopulations

African (AFR)

AF:

0.0000842

AC:

AN:

11876

American (AMR)

AF:

0.00

AC:

AN:

791

Ashkenazi Jewish (ASJ)

AF:

0.00158

AC:

AN:

3788

East Asian (EAS)

AF:

0.00

AC:

AN:

2903

South Asian (SAS)

AF:

0.00

AC:

AN:

11264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

261

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1024

European-Non Finnish (NFE)

AF:

0.000197

AC:

110

AN:

557654

Other (OTH)

AF:

0.000397

AC:

AN:

20156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000294

AC:

AN:

105582

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

AN XY:

29058

show subpopulations

African (AFR)

AF:

0.0000697

AC:

AN:

28695

American (AMR)

AF:

0.000102

AC:

AN:

9770

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

2605

East Asian (EAS)

AF:

0.00

AC:

AN:

3447

South Asian (SAS)

AF:

0.00

AC:

AN:

2372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

205

European-Non Finnish (NFE)

AF:

0.000232

AC:

AN:

51750

Other (OTH)

AF:

0.000701

AC:

AN:

1427

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000317

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 18, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

3.3

PromoterAI

-0.0040

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over