rs114115159
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004517.4(ILK):āc.65A>Gā(p.Asn22Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,611,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00081 ( 1 hom., cov: 32)
Exomes š: 0.0012 ( 3 hom. )
Consequence
ILK
NM_004517.4 missense
NM_004517.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 8.44
Genes affected
ILK (HGNC:6040): (integrin linked kinase) This gene encodes a protein with a kinase-like domain and four ankyrin-like repeats. The encoded protein associates at the cell membrane with the cytoplasmic domain of beta integrins, where it regulates integrin-mediated signal transduction. Activity of this protein is important in the epithelial to mesenchymal transition, and over-expression of this gene is implicated in tumor growth and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.019182503).
BP6
?
Variant 11-6604336-A-G is Benign according to our data. Variant chr11-6604336-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 201788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6604336-A-G is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 123 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ILK | NM_004517.4 | c.65A>G | p.Asn22Ser | missense_variant | 2/13 | ENST00000299421.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ILK | ENST00000299421.9 | c.65A>G | p.Asn22Ser | missense_variant | 2/13 | 1 | NM_004517.4 | P1 | |
ENST00000527191.1 | n.85T>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000808 AC: 123AN: 152216Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00115 AC: 281AN: 243902Hom.: 0 AF XY: 0.00117 AC XY: 155AN XY: 132336
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GnomAD4 exome AF: 0.00121 AC: 1766AN: 1459338Hom.: 3 Cov.: 30 AF XY: 0.00119 AC XY: 867AN XY: 725732
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GnomAD4 genome ? AF: 0.000807 AC: 123AN: 152334Hom.: 1 Cov.: 32 AF XY: 0.000698 AC XY: 52AN XY: 74506
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ExAC
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Asia WGS
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 18, 2015 | p.Asn22Ser in exon 1 of ILK: This variant is not expected to have clinical signi ficance because it has been identified in 0.3% (151/47102) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs114115159). - |
Uncertain significance, no assertion criteria provided | clinical testing | Stanford Center for Inherited Cardiovascular Disease, Stanford University | Jun 12, 2015 | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. ILK p.Asn22Ser Given lack of case data and the presence in the general population, we consider this variant a variant of uncertain significance. The variant has not been reported in association with disease. In silico analysis is inconsistent. The variant was reported online in 158 of 42181 individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of June 11th, 2015). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Sep 08, 2017 | - - |
Primary familial hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
ILK-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 16, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;N;N;.;.
REVEL
Benign
Sift
Benign
T;.;T;T;T;.;.
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
P;.;P;.;P;.;.
Vest4
MVP
MPC
0.36
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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