rs61752970
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000276.4(OCRL):c.41C>T(p.Thr14Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,205,712 control chromosomes in the GnomAD database, including 23 homozygotes. There are 2,616 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. T14A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000276.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCRL | NM_000276.4 | c.41C>T | p.Thr14Ile | missense_variant, splice_region_variant | 2/24 | ENST00000371113.9 | |
OCRL | NM_001318784.2 | c.44C>T | p.Thr15Ile | missense_variant | 2/24 | ||
OCRL | NM_001587.4 | c.41C>T | p.Thr14Ile | missense_variant, splice_region_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCRL | ENST00000371113.9 | c.41C>T | p.Thr14Ile | missense_variant, splice_region_variant | 2/24 | 1 | NM_000276.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00482 AC: 534AN: 110771Hom.: 2 Cov.: 22 AF XY: 0.00449 AC XY: 148AN XY: 32975
GnomAD3 exomes AF: 0.00565 AC: 1036AN: 183264Hom.: 3 AF XY: 0.00612 AC XY: 415AN XY: 67778
GnomAD4 exome AF: 0.00710 AC: 7775AN: 1094892Hom.: 21 Cov.: 30 AF XY: 0.00685 AC XY: 2468AN XY: 360456
GnomAD4 genome ? AF: 0.00482 AC: 534AN: 110820Hom.: 2 Cov.: 22 AF XY: 0.00448 AC XY: 148AN XY: 33034
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 15, 2017 | - - |
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 11, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 12, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Lowe syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Nephrolithiasis/nephrocalcinosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2017 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at