rs78215631
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_006267.5(RANBP2):c.3033G>A(p.Pro1011Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000849 in 1,614,020 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0044 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00048 ( 5 hom. )
Consequence
RANBP2
NM_006267.5 synonymous
NM_006267.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.166
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 2-108763572-G-A is Benign according to our data. Variant chr2-108763572-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.166 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000476 (696/1461840) while in subpopulation AFR AF= 0.0168 (562/33474). AF 95% confidence interval is 0.0156. There are 5 homozygotes in gnomad4_exome. There are 294 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 675 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RANBP2 | ENST00000283195.11 | c.3033G>A | p.Pro1011Pro | synonymous_variant | Exon 20 of 29 | 1 | NM_006267.5 | ENSP00000283195.6 | ||
| RANBP2 | ENST00000697737.1 | c.2602+5024G>A | intron_variant | Intron 18 of 26 | ENSP00000513426.1 | |||||
| RANBP2 | ENST00000697740.1 | c.2524+5024G>A | intron_variant | Intron 18 of 26 | ENSP00000513427.1 |
Frequencies
GnomAD3 genomes 0.00444 AC: 675AN: 152062Hom.: 4 Cov.: 31
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GnomAD3 exomes AF: 0.00109 AC: 275AN: 251194Hom.: 0 AF XY: 0.000832 AC XY: 113AN XY: 135756
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GnomAD4 exome AF: 0.000476 AC: 696AN: 1461840Hom.: 5 Cov.: 34 AF XY: 0.000404 AC XY: 294AN XY: 727214
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GnomAD4 genome 0.00444 AC: 675AN: 152180Hom.: 4 Cov.: 31 AF XY: 0.00399 AC XY: 297AN XY: 74404
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Mar 27, 2017
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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. -
Familial acute necrotizing encephalopathy Benign:1
Oct 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at