chrX-28789402-A-G
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2
The NM_014271.4(IL1RAPL1):āc.59A>Gā(p.Lys20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,205,692 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000045 ( 0 hom., 2 hem., cov: 23)
Exomes š: 0.000058 ( 0 hom. 19 hem. )
Consequence
IL1RAPL1
NM_014271.4 missense
NM_014271.4 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 6.79
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 -7 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.34103692).
BP6
Variant X-28789402-A-G is Benign according to our data. Variant chrX-28789402-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3067362.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL1RAPL1 | NM_014271.4 | c.59A>G | p.Lys20Arg | missense_variant | 2/11 | ENST00000378993.6 | |
IL1RAPL1 | XM_017029240.2 | c.59A>G | p.Lys20Arg | missense_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RAPL1 | ENST00000378993.6 | c.59A>G | p.Lys20Arg | missense_variant | 2/11 | 1 | NM_014271.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000446 AC: 5AN: 112150Hom.: 0 Cov.: 23 AF XY: 0.0000583 AC XY: 2AN XY: 34302
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GnomAD3 exomes AF: 0.0000982 AC: 18AN: 183376Hom.: 0 AF XY: 0.0000590 AC XY: 4AN XY: 67842
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GnomAD4 exome AF: 0.0000576 AC: 63AN: 1093542Hom.: 0 Cov.: 28 AF XY: 0.0000529 AC XY: 19AN XY: 359062
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GnomAD4 genome AF: 0.0000446 AC: 5AN: 112150Hom.: 0 Cov.: 23 AF XY: 0.0000583 AC XY: 2AN XY: 34302
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | IL1RAPL1: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of methylation at K20 (P = 0.0231);
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at