rs569709951
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001134363.3(RBM20):c.348C>T(p.Ala116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,551,706 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 synonymous
NM_001134363.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 10-110780957-C-T is Benign according to our data. Variant chr10-110780957-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110780957-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.348C>T | p.Ala116= | synonymous_variant | 2/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.183C>T | p.Ala61= | synonymous_variant | 2/14 | ||
RBM20 | XM_017016104.3 | c.-37C>T | 5_prime_UTR_variant | 2/14 | |||
RBM20 | XM_047425116.1 | c.-37C>T | 5_prime_UTR_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.348C>T | p.Ala116= | synonymous_variant | 2/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 5AN: 156584Hom.: 0 AF XY: 0.0000362 AC XY: 3AN XY: 82982
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GnomAD4 exome AF: 0.000109 AC: 153AN: 1399430Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 65AN XY: 690220
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 28, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 07, 2016 | p.Ala116Ala in exon 2 of RBM20: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1/8764 European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs569709951). - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jul 27, 2017 | - - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 04, 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
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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