rs139387463
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The ENST00000283195.11(RANBP2):c.9369+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,608,308 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 5 hom. )
Consequence
RANBP2
ENST00000283195.11 splice_donor_region, intron
ENST00000283195.11 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00007117
2
Clinical Significance
Conservation
PhyloP100: 2.28
Genes affected
RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 2-108782866-G-A is Benign according to our data. Variant chr2-108782866-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-108782866-G-A is described in Lovd as [Benign]. Variant chr2-108782866-G-A is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 164 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.9369+4G>A | splice_donor_region_variant, intron_variant | ENST00000283195.11 | NP_006258.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.9369+4G>A | splice_donor_region_variant, intron_variant | 1 | NM_006267.5 | ENSP00000283195 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00108 AC: 164AN: 152070Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00112 AC: 276AN: 247170Hom.: 1 AF XY: 0.00114 AC XY: 153AN XY: 134018
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GnomAD4 exome AF: 0.00182 AC: 2644AN: 1456120Hom.: 5 Cov.: 31 AF XY: 0.00179 AC XY: 1295AN XY: 724800
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GnomAD4 genome AF: 0.00108 AC: 164AN: 152188Hom.: 1 Cov.: 32 AF XY: 0.00112 AC XY: 83AN XY: 74408
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2018 | 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. - |
not provided Benign:2
Likely 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 | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | RANBP2: BS1, BS2 - |
Familial acute necrotizing encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 28, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at