rs150250182
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001199799.2(ILDR1):āc.1159T>Cā(p.Ser387Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,122 control chromosomes in the GnomAD database, including 3 homozygotes. 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. S387C) has been classified as Likely benign.
Frequency
Consequence
NM_001199799.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ILDR1 | NM_001199799.2 | c.1159T>C | p.Ser387Pro | missense_variant | 7/8 | ENST00000344209.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ILDR1 | ENST00000344209.10 | c.1159T>C | p.Ser387Pro | missense_variant | 7/8 | 1 | NM_001199799.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000329 AC: 50AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000477 AC: 120AN: 251480Hom.: 0 AF XY: 0.000537 AC XY: 73AN XY: 135914
GnomAD4 exome AF: 0.000317 AC: 464AN: 1461892Hom.: 3 Cov.: 41 AF XY: 0.000391 AC XY: 284AN XY: 727248
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 387 of the ILDR1 protein (p.Ser387Pro). This variant is present in population databases (rs150250182, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ILDR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 178382). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2021 | This variant is associated with the following publications: (PMID: 28322503) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 18, 2016 | p.Ser387Pro 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 this variant (Pro) at this position. In addition, computational prediction t ools do not suggest a high likelihood of impact to the protein, and it has been across several populations with a highest frequency of 0.1% (19/16512) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs150250182). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at