rs143785916
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_001134363.3(RBM20):c.1922G>A(p.Arg641Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,550,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R641W) has been classified as Likely benign.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1922G>A | p.Arg641Gln | missense_variant | 9/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1757G>A | p.Arg586Gln | missense_variant | 9/14 | ||
RBM20 | XM_017016104.3 | c.1538G>A | p.Arg513Gln | missense_variant | 9/14 | ||
RBM20 | XM_047425116.1 | c.1538G>A | p.Arg513Gln | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1922G>A | p.Arg641Gln | missense_variant | 9/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000337 AC: 52AN: 154436Hom.: 0 AF XY: 0.000256 AC XY: 21AN XY: 82114
GnomAD4 exome AF: 0.000109 AC: 152AN: 1398662Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 73AN XY: 689744
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74414
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 15, 2019 | The RBM20 c.1922G>A; p.Arg641Gln variant (rs143785916), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 202064). This variant is found in the East Asian population with an allele frequency of 0.45% (56/12330 alleles) in the Genome Aggregation Database. The arginine at codon 641 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Arg641Gln variant is uncertain at this time. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 13, 2016 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2020 | This alteration is classified as likely 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