X-28789368-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014271.4(IL1RAPL1):​c.25A>G​(p.Ile9Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000146 in 1,096,044 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000015 ( 0 hom. 7 hem. )

Consequence

IL1RAPL1
NM_014271.4 missense

Scores

1
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16469291).
BS2
High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPL1NM_014271.4 linkuse as main transcriptc.25A>G p.Ile9Val missense_variant 2/11 ENST00000378993.6
IL1RAPL1XM_017029240.2 linkuse as main transcriptc.25A>G p.Ile9Val missense_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPL1ENST00000378993.6 linkuse as main transcriptc.25A>G p.Ile9Val missense_variant 2/111 NM_014271.4 P1Q9NZN1-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.0000146
AC:
16
AN:
1096044
Hom.:
0
Cov.:
29
AF XY:
0.0000194
AC XY:
7
AN XY:
361526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000190
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 29, 2023In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. This variant has not been reported in the literature in individuals affected with IL1RAPL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 9 of the IL1RAPL1 protein (p.Ile9Val). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.18
T
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.99
N;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.059
Sift
Benign
0.14
T
Sift4G
Benign
0.45
T
Polyphen
0.028
B
Vest4
0.30
MutPred
0.29
Gain of loop (P = 0.2045);
MVP
0.50
MPC
0.71
ClinPred
0.19
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-28807485; API