rs746732835
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001199799.2(ILDR1):c.1160C>G(p.Ser387Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S387P) has been classified as Likely benign.
Frequency
Consequence
NM_001199799.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ILDR1 | NM_001199799.2 | c.1160C>G | p.Ser387Cys | missense_variant | 7/8 | ENST00000344209.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ILDR1 | ENST00000344209.10 | c.1160C>G | p.Ser387Cys | missense_variant | 7/8 | 1 | NM_001199799.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251482Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135914
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461892Hom.: 0 Cov.: 41 AF XY: 0.0000303 AC XY: 22AN XY: 727248
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 517165). This variant has not been reported in the literature in individuals affected with ILDR1-related conditions. This variant is present in population databases (rs746732835, gnomAD 0.1%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 387 of the ILDR1 protein (p.Ser387Cys). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 22, 2016 | p.Ser387Cys in exon 7 of ILDR1: This variant is not expected to have clinical si gnificance due to a lack of conservation across species with several mammals hav ing a cysteine (Cys) at this position. In addition, computational prediction too ls do not suggest a high likelihood of impact to the protein and this variant ha s been identified in 4/11574 Latino chromosomes and 6/66734 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs746732835). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at