X-154018741-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001569.4(IRAK1):c.587T>C(p.Phe196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.83 ( 28339 hom., 24998 hem., cov: 21)
Exomes 𝑓: 0.81 ( 227179 hom. 218495 hem. )
Failed GnomAD Quality Control
Consequence
IRAK1
NM_001569.4 missense
NM_001569.4 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 2.94
Genes affected
IRAK1 (HGNC:6112): (interleukin 1 receptor associated kinase 1) This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=1.6834772E-6).
BP6
Variant X-154018741-A-G is Benign according to our data. Variant chrX-154018741-A-G is described in ClinVar as [Benign]. Clinvar id is 2688060.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRAK1 | NM_001569.4 | c.587T>C | p.Phe196Ser | missense_variant | 5/14 | ENST00000369980.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRAK1 | ENST00000369980.8 | c.587T>C | p.Phe196Ser | missense_variant | 5/14 | 1 | NM_001569.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.829 AC: 90140AN: 108668Hom.: 28337 Cov.: 21 AF XY: 0.806 AC XY: 24939AN XY: 30934
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GnomAD3 exomes AF: 0.716 AC: 129023AN: 180099Hom.: 32457 AF XY: 0.714 AC XY: 46671AN XY: 65321
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.814 AC: 753155AN: 924891Hom.: 227179 Cov.: 20 AF XY: 0.799 AC XY: 218495AN XY: 273467
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GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.830 AC: 90196AN: 108722Hom.: 28339 Cov.: 21 AF XY: 0.806 AC XY: 24998AN XY: 30998
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MPC
ClinPred
T
GERP RS
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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