chrX-28789325-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_014271.4(IL1RAPL1):c.-19G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.63 ( 17099 hom., 20472 hem., cov: 23)
Exomes 𝑓: 0.52 ( 99590 hom. 169950 hem. )
Failed GnomAD Quality Control
Consequence
IL1RAPL1
NM_014271.4 5_prime_UTR
NM_014271.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.755
Genes affected
IL1RAPL1 (HGNC:5996): (interleukin 1 receptor accessory protein like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family and is similar to the interleukin 1 accessory proteins. This protein has an N-terminal signal peptide, three extracellular immunoglobulin Ig-like domains, a transmembrane domain, an intracellular Toll/IL-1R domain, and a long C-terminal tail which interacts with multiple signalling molecules. This gene is located at a region on chromosome X that is associated with a non-syndromic form of X-linked intellectual disability. Deletions and mutations in this gene were found in patients with intellectual disability. This gene is expressed at a high level in post-natal brain structures involved in the hippocampal memory system, which suggests a specialized role in the physiological processes underlying memory and learning abilities, and plays a role in synapse formation and stabilization. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant X-28789325-G-A is Benign according to our data. Variant chrX-28789325-G-A is described in ClinVar as [Benign]. Clinvar id is 281021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-28789325-G-A is described in Lovd as [Benign]. Variant chrX-28789325-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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IL1RAPL1 | NM_014271.4 | c.-19G>A | 5_prime_UTR_variant | 2/11 | ENST00000378993.6 | ||
IL1RAPL1 | XM_017029240.2 | c.-19G>A | 5_prime_UTR_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RAPL1 | ENST00000378993.6 | c.-19G>A | 5_prime_UTR_variant | 2/11 | 1 | NM_014271.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.632 AC: 69709AN: 110355Hom.: 17086 Cov.: 23 AF XY: 0.627 AC XY: 20430AN XY: 32589
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GnomAD3 exomes AF: 0.585 AC: 105986AN: 181267Hom.: 21364 AF XY: 0.574 AC XY: 37857AN XY: 65911
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.524 AC: 539644AN: 1028904Hom.: 99590 Cov.: 20 AF XY: 0.538 AC XY: 169950AN XY: 315748
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GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.632 AC: 69766AN: 110401Hom.: 17099 Cov.: 23 AF XY: 0.627 AC XY: 20472AN XY: 32645
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 11, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Intellectual disability, X-linked 21 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at