rs727503097
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000344209.10(ILDR1):c.1360G>A(p.Glu454Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000344209.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ILDR1 | NM_001199799.2 | c.1360G>A | p.Glu454Lys | missense_variant | 7/8 | ENST00000344209.10 | NP_001186728.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ILDR1 | ENST00000344209.10 | c.1360G>A | p.Glu454Lys | missense_variant | 7/8 | 1 | NM_001199799.2 | ENSP00000345667 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248720Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134762
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460790Hom.: 0 Cov.: 41 AF XY: 0.0000110 AC XY: 8AN XY: 726558
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 25, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Glu454Lys var iant in ILDR has now been identified by our laboratory in two individuals with h earing loss, but a variant affecting the remaining copy of ILDR1 was not identif ied in either one. This variant has been identified in 2/64670 European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs727503097); however, this frequency is not high enough to rule out a path ogenic role. The glutamic acid (Glu) at position 454 is not conserved in mammals or evolutionary distant species, raising the possibility that a change at this position may be tolerated. Additional computational prediction tools suggest tha t this variant may not impact the protein, though this information is not predic tive enough to rule out pathogenicity. In summary, while the clinical significan ce of the p.Glu454Lys variant is uncertain, available data suggest that it is mo re likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at