rs187915202
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001134363.3(RBM20):c.2655+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 1,525,998 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 31 hom. )
Consequence
RBM20
NM_001134363.3 intron
NM_001134363.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.222
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 10-110820191-A-G is Benign according to our data. Variant chr10-110820191-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43993.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=4, Uncertain_significance=1}. Variant chr10-110820191-A-G is described in Lovd as [Benign]. Variant chr10-110820191-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00423 (645/152334) while in subpopulation NFE AF= 0.00685 (466/68032). AF 95% confidence interval is 0.00634. There are 0 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 645 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.2655+15A>G | intron_variant | ENST00000369519.4 | |||
RBM20 | XM_017016103.3 | c.2490+15A>G | intron_variant | ||||
RBM20 | XM_017016104.3 | c.2271+15A>G | intron_variant | ||||
RBM20 | XM_047425116.1 | c.2271+15A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.2655+15A>G | intron_variant | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00424 AC: 645AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00403 AC: 628AN: 155940Hom.: 3 AF XY: 0.00381 AC XY: 315AN XY: 82688
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GnomAD4 exome AF: 0.00589 AC: 8089AN: 1373664Hom.: 31 Cov.: 24 AF XY: 0.00571 AC XY: 3881AN XY: 679186
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:10
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 17, 2013 | 2655+15A>G in intron 10 of RBM20: This variant is not expected to have clinical significance because it has been identified in 0.3% (10/3182) of European Americ an chromosomes and 0.15% (2/1384) of African American chromosomes by the NHLBI E xome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs187915202). 2655+15A>G in intron 10 of RBM20: rs187915202; allele frequency = 0.3 (10/3182 ) ** - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 28, 2022 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Dilated cardiomyopathy 1DD Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 15, 2019 | - - |
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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | RBM20: BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at