rs730880185
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2
The NM_001134363.3(RBM20):c.2565_2570del(p.Gln856_Glu857del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000342 in 1,549,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 inframe_deletion
NM_001134363.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.00
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001134363.3.
BP6
?
Variant 10-110820081-GAGGAAC-G is Benign according to our data. Variant chr10-110820081-GAGGAAC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43992.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}. Variant chr10-110820081-GAGGAAC-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000788 (12/152306) while in subpopulation EAS AF= 0.00231 (12/5188). AF 95% confidence interval is 0.00133. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.2565_2570del | p.Gln856_Glu857del | inframe_deletion | 10/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.2400_2405del | p.Gln801_Glu802del | inframe_deletion | 10/14 | ||
RBM20 | XM_017016104.3 | c.2181_2186del | p.Gln728_Glu729del | inframe_deletion | 10/14 | ||
RBM20 | XM_047425116.1 | c.2181_2186del | p.Gln728_Glu729del | inframe_deletion | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.2565_2570del | p.Gln856_Glu857del | inframe_deletion | 10/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000173 AC: 27AN: 155640Hom.: 0 AF XY: 0.000146 AC XY: 12AN XY: 82396
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GnomAD4 exome AF: 0.0000294 AC: 41AN: 1396758Hom.: 0 AF XY: 0.0000218 AC XY: 15AN XY: 688946
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74476
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 02, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 09, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Gln856_Glu857de l variant in RBM20 has not been reported in the literature but has been identifi ed in one infant with LVNC. This variant creates an in-frame deletion of 2 amino acids but the impact of this deletion on the protein remains unknown. In summar y, additional information is needed to fully assess the clinical significance of the Gln856_Glu857del variant. - |
Ventricular fibrillation, paroxysmal familial, type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Sep 24, 2014 | - - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Jul 06, 2017 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 23, 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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Find out detailed SpliceAI scores and Pangolin per-transcript scores at