X-28789404-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_014271.4(IL1RAPL1):c.61G>T(p.Val21Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,204,845 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )
Consequence
IL1RAPL1
NM_014271.4 missense
NM_014271.4 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 7.27
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 Likely_benign. Variant got -4 ACMG points.
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.61G>T | p.Val21Phe | missense_variant | 2/11 | ENST00000378993.6 | |
IL1RAPL1 | XM_017029240.2 | c.61G>T | p.Val21Phe | missense_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RAPL1 | ENST00000378993.6 | c.61G>T | p.Val21Phe | missense_variant | 2/11 | 1 | NM_014271.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000893 AC: 1AN: 112016Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34182
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GnomAD4 exome AF: 0.00000275 AC: 3AN: 1092775Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 358315
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GnomAD4 genome AF: 0.0000178 AC: 2AN: 112070Hom.: 0 Cov.: 23 AF XY: 0.0000584 AC XY: 2AN XY: 34246
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of helix (P = 0.0033);
MVP
MPC
ClinPred
D
GERP RS
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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