rs1553496153
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_006267.5(RANBP2):āc.4950A>Gā(p.Thr1650Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,600 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 (ā ).
Frequency
Genomes: not found (cov: 11)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
RANBP2
NM_006267.5 synonymous
NM_006267.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.254
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 2-108765489-A-G is Benign according to our data. Variant chr2-108765489-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 469465.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.254 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.4950A>G | p.Thr1650Thr | synonymous_variant | 20/29 | 1 | NM_006267.5 | ENSP00000283195.6 | ||
RANBP2 | ENST00000697737.1 | c.2603-6212A>G | intron_variant | ENSP00000513426.1 | ||||||
RANBP2 | ENST00000697740.1 | c.2525-6212A>G | intron_variant | ENSP00000513427.1 |
Frequencies
GnomAD3 genomes Cov.: 11
GnomAD3 genomes
Cov.:
11
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461600Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727100
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1461600
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33
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1
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727100
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GnomAD4 genome Cov.: 11
GnomAD4 genome
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11
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial acute necrotizing encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 02, 2020 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
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