2-162282494-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022168.4(IFIH1):āc.1178A>Gā(p.Asp393Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,778 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
IFIH1
NM_022168.4 missense
NM_022168.4 missense
Scores
1
10
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.60
Genes affected
IFIH1 (HGNC:18873): (interferon induced with helicase C domain 1) IFIH1 encodes MDA5 which is an intracellular sensor of viral RNA that triggers the innate immune response. Sensing RNA length and secondary structure, MDA5 binds dsRNA oligonucleotides with a modified DExD/H-box helicase core and a C-terminal domain, thus leading to a proinflammatory response that includes interferons. It has been shown that Coronaviruses (CoVs) as well as various other virus families, are capable of evading the MDA5-dependent interferon response, thus impeding the activation of the innate immune response to infection. MDA5 has also been shown to play an important role in enhancing natural killer cell function in malaria infection. In addition to its protective role in antiviral responses, MDA5 has been implicated in autoimmune and autoinflammatory diseases such as type 1 diabetes, systemic lupus erythematosus, and Aicardi-Goutieres syndrome[provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFIH1 | NM_022168.4 | c.1178A>G | p.Asp393Gly | missense_variant | 6/16 | ENST00000649979.2 | NP_071451.2 | |
IFIH1 | XM_047445407.1 | c.461A>G | p.Asp154Gly | missense_variant | 5/15 | XP_047301363.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFIH1 | ENST00000649979.2 | c.1178A>G | p.Asp393Gly | missense_variant | 6/16 | NM_022168.4 | ENSP00000497271 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249814Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135064
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459778Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726244
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GnomAD4 genome Cov.: 32
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;.
REVEL
Benign
Sift
Uncertain
.;D;.
Sift4G
Uncertain
.;D;.
Polyphen
D;D;.
Vest4
0.66
MutPred
Gain of MoRF binding (P = 0.0724);Gain of MoRF binding (P = 0.0724);Gain of MoRF binding (P = 0.0724);
MVP
0.71
MPC
0.21
ClinPred
D
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