rs145995735
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_003383.5(VLDLR):āc.732C>Gā(p.Ile244Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,614,190 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I244I) has been classified as Likely benign.
Frequency
Consequence
NM_003383.5 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 |
---|---|---|---|---|---|---|---|
VLDLR | NM_003383.5 | c.732C>G | p.Ile244Met | missense_variant | 5/19 | ENST00000382100.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VLDLR | ENST00000382100.8 | c.732C>G | p.Ile244Met | missense_variant | 5/19 | 1 | NM_003383.5 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000481 AC: 121AN: 251378Hom.: 1 AF XY: 0.000515 AC XY: 70AN XY: 135856
GnomAD4 exome AF: 0.000406 AC: 593AN: 1461876Hom.: 2 Cov.: 31 AF XY: 0.000454 AC XY: 330AN XY: 727236
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74484
ClinVar
Submissions by phenotype
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Brain Gene Registry | - | Variant classified as Uncertain significance and reported on 12-06-2012 by Baylor College of Medicine. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 05, 2021 | This variant is associated with the following publications: (PMID: 33111339) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 10, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2022 | The c.732C>G (p.I244M) alteration is located in exon 5 (coding exon 5) of the VLDLR gene. This alteration results from a C to G substitution at nucleotide position 732, causing the isoleucine (I) at amino acid position 244 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital cerebellar hypoplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at