rs200833729
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_022168.4(IFIH1):c.2597C>T(p.Pro866Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,611,814 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P866S) has been classified as Uncertain significance.
Frequency
Consequence
NM_022168.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFIH1 | NM_022168.4 | c.2597C>T | p.Pro866Leu | missense_variant | 13/16 | ENST00000649979.2 | |
IFIH1 | XM_047445407.1 | c.1880C>T | p.Pro627Leu | missense_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFIH1 | ENST00000649979.2 | c.2597C>T | p.Pro866Leu | missense_variant | 13/16 | NM_022168.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000270 AC: 41AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000398 AC: 99AN: 248756Hom.: 0 AF XY: 0.000476 AC XY: 64AN XY: 134478
GnomAD4 exome AF: 0.000325 AC: 474AN: 1459624Hom.: 6 Cov.: 30 AF XY: 0.000353 AC XY: 256AN XY: 726014
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74414
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2020 | - - |
Aicardi-Goutieres syndrome 7;C4225427:Singleton-Merten syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
IFIH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at