chrX-28789355-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_014271.4(IL1RAPL1):c.12G>A(p.Pro4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,206,504 control chromosomes in the GnomAD database, including 6 homozygotes. There are 587 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 0.0013 ( 1 hom., 39 hem., cov: 23)
Exomes 𝑓: 0.0014 ( 5 hom. 548 hem. )
Consequence
IL1RAPL1
NM_014271.4 synonymous
NM_014271.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.146
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant X-28789355-G-A is Benign according to our data. Variant chrX-28789355-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.146 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 39 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL1RAPL1 | NM_014271.4 | c.12G>A | p.Pro4= | synonymous_variant | 2/11 | ENST00000378993.6 | |
IL1RAPL1 | XM_017029240.2 | c.12G>A | p.Pro4= | synonymous_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RAPL1 | ENST00000378993.6 | c.12G>A | p.Pro4= | synonymous_variant | 2/11 | 1 | NM_014271.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00125 AC: 140AN: 111847Hom.: 1 Cov.: 23 AF XY: 0.00115 AC XY: 39AN XY: 34023
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GnomAD3 exomes AF: 0.00152 AC: 278AN: 183256Hom.: 2 AF XY: 0.00165 AC XY: 112AN XY: 67730
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GnomAD4 exome AF: 0.00141 AC: 1547AN: 1094604Hom.: 5 Cov.: 28 AF XY: 0.00152 AC XY: 548AN XY: 360198
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GnomAD4 genome AF: 0.00125 AC: 140AN: 111900Hom.: 1 Cov.: 23 AF XY: 0.00114 AC XY: 39AN XY: 34086
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2019 | - - |
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2012 | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Intellectual disability, X-linked 21 Benign:1
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