Variant X-49250661-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014009.4(FOXP3):c.*673G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 281,687 control chromosomes in the GnomAD database, including 16 homozygotes. There are 357 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 12 hom., 262 hem., cov: 24)

Exomes 𝑓: 0.0021 ( 4 hom. 95 hem. )

Consequence

FOXP3
NM_014009.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.02

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant X-49250661-C-T is Benign according to our data. Variant chrX-49250661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00864 (970/112312) while in subpopulation AFR AF= 0.0276 (853/30901). AF 95% confidence interval is 0.0261. There are 12 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP3	NM_014009.4 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant	12/12	ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant	11/11		NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant	12/12	1	NM_014009.4	ENSP00000365380	P1	Q9BZS1-1

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

965

AN:

112258

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

260

AN XY:

34454

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00357

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000368

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0333

Gnomad NFE

AF:

0.000940

Gnomad OTH

AF:

0.0125

GnomAD4 exome

AF:

0.00210

AC:

355

AN:

169375

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

AN XY:

56069

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00864

AC:

970

AN:

112312

Hom.:

Cov.:

AF XY:

0.00759

AC XY:

262

AN XY:

34518

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.00356

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000369

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000940

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00664

Hom.:

Bravo

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.034

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over