rs397516593
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001134363.3(RBM20):c.128_130dup(p.Gln43dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00133 in 1,525,996 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00089 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 36 hom. )
Consequence
RBM20
NM_001134363.3 inframe_insertion
NM_001134363.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 10-110644576-T-TGCA is Benign according to our data. Variant chr10-110644576-T-TGCA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43970.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=2, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000894 (135/151004) while in subpopulation SAS AF= 0.0253 (120/4740). AF 95% confidence interval is 0.0216. There are 3 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 135 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.128_130dup | p.Gln43dup | inframe_insertion | 1/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.26+1142_26+1144dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.128_130dup | p.Gln43dup | inframe_insertion | 1/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000901 AC: 136AN: 150884Hom.: 3 Cov.: 32
GnomAD3 genomes
AF:
AC:
136
AN:
150884
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00393 AC: 476AN: 121236Hom.: 9 AF XY: 0.00520 AC XY: 348AN XY: 66978
GnomAD3 exomes
AF:
AC:
476
AN:
121236
Hom.:
AF XY:
AC XY:
348
AN XY:
66978
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00138 AC: 1892AN: 1374992Hom.: 36 Cov.: 33 AF XY: 0.00197 AC XY: 1336AN XY: 678152
GnomAD4 exome
AF:
AC:
1892
AN:
1374992
Hom.:
Cov.:
33
AF XY:
AC XY:
1336
AN XY:
678152
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000894 AC: 135AN: 151004Hom.: 3 Cov.: 32 AF XY: 0.00141 AC XY: 104AN XY: 73762
GnomAD4 genome
AF:
AC:
135
AN:
151004
Hom.:
Cov.:
32
AF XY:
AC XY:
104
AN XY:
73762
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Asia WGS
AF:
AC:
32
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 11, 2015 | p.Gln43_Pro44insGln in exon 1 of RBM20: This variant is not expected to have cli nical significance because it has been identified in 2.0% (133/6770) of South As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs397516593). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2022 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiomyopathy Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2014 | The c.128_130dupAGC variant in the RBM20 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. This in-frame duplication does not occur in any of the domains thought to be critical to protein structure/function including Proline-rich domains, Glutamine-rich domains, or in the RNA Recognition Motif (RRM). The NHLBI ESP Exome Variant Server reports c.128_130dupAGC was not observed in approximately 2000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. However, population data from ethnically-matched backgrounds was not available at the time of this report. With the clinical and molecular information available at this time, we cannot definitively determine if c.128_130dupAGC is a disease-causing mutation or a rare benign variant. The variant is found in DCM,DCM-CRDM panel(s). - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 20, 2017 | - - |
Dilated Cardiomyopathy, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Dilated cardiomyopathy 1DD Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 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:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at