19-4818283-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_182919.4(TICAM1):c.95C>T(p.Thr32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,612,904 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 48 hom. )
Consequence
TICAM1
NM_182919.4 missense
NM_182919.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 0.0660
Genes affected
TICAM1 (HGNC:18348): (TIR domain containing adaptor molecule 1) This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. This protein is involved in native immunity against invading pathogens. It specifically interacts with toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B, during an antiviral immune response. Mutations in this gene are associated with encephalopathy, acute, infection-induced. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0027892292).
BP6
Variant 19-4818283-G-A is Benign according to our data. Variant chr19-4818283-G-A is described in ClinVar as [Benign]. Clinvar id is 540521.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00141 (215/152320) while in subpopulation EAS AF= 0.0357 (185/5182). AF 95% confidence interval is 0.0315. There are 2 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TICAM1 | NM_182919.4 | c.95C>T | p.Thr32Ile | missense_variant | 2/2 | ENST00000248244.6 | NP_891549.1 | |
TICAM1 | NM_001385678.1 | c.53C>T | p.Thr18Ile | missense_variant | 3/3 | NP_001372607.1 | ||
TICAM1 | NM_001385679.1 | c.-41C>T | 5_prime_UTR_variant | 2/2 | NP_001372608.1 | |||
TICAM1 | NM_001385680.1 | c.-72+101C>T | intron_variant | NP_001372609.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TICAM1 | ENST00000248244.6 | c.95C>T | p.Thr32Ile | missense_variant | 2/2 | 1 | NM_182919.4 | ENSP00000248244.4 |
Frequencies
GnomAD3 genomes AF: 0.00142 AC: 216AN: 152202Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00313 AC: 780AN: 249220Hom.: 9 AF XY: 0.00293 AC XY: 396AN XY: 135086
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GnomAD4 exome AF: 0.00147 AC: 2144AN: 1460584Hom.: 48 Cov.: 80 AF XY: 0.00147 AC XY: 1066AN XY: 726620
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GnomAD4 genome AF: 0.00141 AC: 215AN: 152320Hom.: 2 Cov.: 32 AF XY: 0.00173 AC XY: 129AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
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MPC
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T
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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