chrX-49250661-C-T

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

2

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]

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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
FOXP3NM_014009.4 linkuse as main transcriptc.*673G>A 3_prime_UTR_variant 12/12 ENST00000376207.10 NP_054728.2
FOXP3NM_001114377.2 linkuse as main transcriptc.*673G>A 3_prime_UTR_variant 11/11 NP_001107849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXP3ENST00000376207.10 linkuse as main transcriptc.*673G>A 3_prime_UTR_variant 12/121 NM_014009.4 ENSP00000365380 P1Q9BZS1-1

Frequencies

GnomAD3 genomes
AF:
0.00860
AC:
965
AN:
112258
Hom.:
12
Cov.:
24
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.:
4
Cov.:
0
AF XY:
0.00169
AC XY:
95
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.:
12
Cov.:
24
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.:
25
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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough 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.

Other links and lift over

dbSNP: rs148013438; hg19: chrX-49107122; API