chr4-1002713-GC-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000203.5(IDUA):c.1190-10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,358,110 control chromosomes in the GnomAD database, including 112 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 51 hom., cov: 29)
Exomes 𝑓: 0.0025 ( 61 hom. )
Consequence
IDUA
NM_000203.5 intron
NM_000203.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.792
Genes affected
IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 4-1002713-GC-G is Benign according to our data. Variant chr4-1002713-GC-G is described in ClinVar as [Benign]. Clinvar id is 496833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1002713-GC-G is described in Lovd as [Benign]. Variant chr4-1002713-GC-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (2265/149774) while in subpopulation AFR AF= 0.0494 (2012/40716). AF 95% confidence interval is 0.0476. There are 51 homozygotes in gnomad4. There are 1056 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 51 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDUA | NM_000203.5 | c.1190-10del | intron_variant | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.1190-10del | intron_variant | 2 | NM_000203.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0151 AC: 2254AN: 149676Hom.: 49 Cov.: 29
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GnomAD3 exomes AF: 0.00548 AC: 401AN: 73188Hom.: 6 AF XY: 0.00417 AC XY: 173AN XY: 41468
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GnomAD4 exome AF: 0.00253 AC: 3062AN: 1208336Hom.: 61 Cov.: 24 AF XY: 0.00221 AC XY: 1322AN XY: 598660
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GnomAD4 genome AF: 0.0151 AC: 2265AN: 149774Hom.: 51 Cov.: 29 AF XY: 0.0144 AC XY: 1056AN XY: 73100
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 29, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 19, 2023 | Variant summary: IDUA c.1190-10delC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.0055 in 73188 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in IDUA causing Mucopolysaccharidosis Type 1 phenotype (0.0027), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1190-10delC in individuals affected with Mucopolysaccharidosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Mucopolysaccharidosis type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2019 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at