X-49250661-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP3	NM_014009.4	c.*673G>A		3_prime_UTR_variant	12/12	ENST00000376207.10
FOXP3	NM_001114377.2	c.*673G>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP3	ENST00000376207.10	c.*673G>A		3_prime_UTR_variant	12/12	1	NM_014009.4	P1

Frequencies

GnomAD3 genomes AF: 0.00860 AC: 965 AN: 112258 Hom.: 12 Cov.: 24 AF XY: 0.00755 AC XY: 260 AN XY: 34454

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

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

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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

Other links and lift over

dbSNP: rs148013438; hg19: chrX-49107122;