X-48684427-A-ACC
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The ENST00000376701.5(WAS):c.273+4_273+5insCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,193,108 control chromosomes in the GnomAD database, including 65 homozygotes. There are 792 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
ENST00000376701.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WAS | NM_000377.3 | c.273+10_273+11dupCC | intron_variant | Intron 2 of 11 | ENST00000376701.5 | NP_000368.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00231 AC: 247AN: 107101Hom.: 5 Cov.: 21 AF XY: 0.00258 AC XY: 78AN XY: 30281
GnomAD3 exomes AF: 0.00521 AC: 842AN: 161608Hom.: 29 AF XY: 0.00472 AC XY: 244AN XY: 51748
GnomAD4 exome AF: 0.00210 AC: 2276AN: 1085966Hom.: 60 Cov.: 32 AF XY: 0.00202 AC XY: 716AN XY: 353868
GnomAD4 genome AF: 0.00228 AC: 244AN: 107142Hom.: 5 Cov.: 21 AF XY: 0.00251 AC XY: 76AN XY: 30332
ClinVar
Submissions by phenotype
not specified Benign:4
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Variant summary: WAS c.273+10_273+11dupCC alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0046 in 176885 control chromosomes, predominantly at a frequency of 221 within the East Asian subpopulation in the gnomAD database, including 25 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 62508.24 fold of the estimated maximal expected allele frequency for a pathogenic variant in WAS causing Wiskott-Aldrich Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.273+10_273+11dupCC in individuals affected with Wiskott-Aldrich Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
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not provided Benign:2
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In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 30738478) -
Wiskott-Aldrich syndrome;C1839163:Thrombocytopenia 1;C1845987:X-linked severe congenital neutropenia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at