rs774128939
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001199799.2(ILDR1):c.352C>T(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,562,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000047 ( 1 hom. )
Consequence
ILDR1
NM_001199799.2 missense
NM_001199799.2 missense
Scores
4
9
5
Clinical Significance
Conservation
PhyloP100: 2.20
Genes affected
ILDR1 (HGNC:28741): (immunoglobulin like domain containing receptor 1) This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a disulfide_bond (size 100) in uniprot entity ILDR1_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_001199799.2
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28080943).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ILDR1 | NM_001199799.2 | c.352C>T | p.Arg118Trp | missense_variant | 3/8 | ENST00000344209.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ILDR1 | ENST00000344209.10 | c.352C>T | p.Arg118Trp | missense_variant | 3/8 | 1 | NM_001199799.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000272 AC: 4AN: 146818Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000199 AC: 50AN: 251062Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135734
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GnomAD4 exome AF: 0.0000473 AC: 67AN: 1415544Hom.: 1 Cov.: 34 AF XY: 0.0000426 AC XY: 30AN XY: 703818
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GnomAD4 genome ? AF: 0.0000272 AC: 4AN: 146818Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 1AN XY: 71202
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 118 of the ILDR1 protein (p.Arg118Trp). This variant is present in population databases (rs774128939, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ILDR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 289899). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 30, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2017 | The p.Arg118Trp variant in ILDR1 has not been previously reported in individuals with hearing loss, but has been reported in ClinVar (Variation ID# 289899) as o f uncertain clinical significance. This variant has been identified in 0.2% (53/ 33566) of Latino chromosomes including one homozygote by the Genome Aggregation Database (gnomAD, http://gnomAD.broadinstitute.org; dbSNP rs774128939). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conse rvation analysis suggest that the p.Arg118Trp variant may impact the protein, th ough this information is not predictive enough to determine pathogenicity. In su mmary, the clinical significance of the p.Arg118Trp variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;.;D
Polyphen
D;D;D;D
Vest4
MutPred
Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);
MVP
MPC
0.29
ClinPred
T
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