X-48683512-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000698625.1(WAS):c.-34-308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 204,149 control chromosomes in the GnomAD database, including 91 homozygotes. There are 723 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.023 ( 79 hom., 681 hem., cov: 22)
Exomes 𝑓: 0.0035 ( 12 hom. 42 hem. )
Consequence
WAS
ENST00000698625.1 intron
ENST00000698625.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.177
Genes affected
WAS (HGNC:12731): (WASP actin nucleation promoting factor) The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5' UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant X-48683512-T-C is Benign according to our data. Variant chrX-48683512-T-C is described in ClinVar as [Benign]. Clinvar id is 1265197.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WAS | XM_011543977.3 | c.-34-308T>C | intron_variant | ||||
WAS | XM_017029786.2 | c.-34-308T>C | intron_variant | ||||
WAS | XM_047442432.1 | c.-34-308T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WAS | ENST00000450772.5 | c.-35+149T>C | intron_variant | 3 | |||||
WAS | ENST00000698625.1 | c.-34-308T>C | intron_variant | P2 |
Frequencies
GnomAD3 genomes AF: 0.0233 AC: 2605AN: 111756Hom.: 78 Cov.: 22 AF XY: 0.0201 AC XY: 681AN XY: 33948
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GnomAD4 exome AF: 0.00351 AC: 324AN: 92342Hom.: 12 AF XY: 0.00235 AC XY: 42AN XY: 17866
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GnomAD4 genome AF: 0.0233 AC: 2605AN: 111807Hom.: 79 Cov.: 22 AF XY: 0.0200 AC XY: 681AN XY: 34009
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2019 | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at