rs142514679
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006267.5(RANBP2):āc.1284A>Gā(p.Arg428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000826 in 1,611,984 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00072 ( 0 hom., cov: 32)
Exomes š: 0.00084 ( 2 hom. )
Consequence
RANBP2
NM_006267.5 synonymous
NM_006267.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.07
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 2-108751274-A-G is Benign according to our data. Variant chr2-108751274-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 469427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.07 with no splicing effect.
BS2
?
High AC in GnomAd4 at 110 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.1284A>G | p.Arg428= | synonymous_variant | 10/29 | ENST00000283195.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.1284A>G | p.Arg428= | synonymous_variant | 10/29 | 1 | NM_006267.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000723 AC: 110AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000777 AC: 194AN: 249550Hom.: 1 AF XY: 0.000775 AC XY: 105AN XY: 135496
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GnomAD4 exome AF: 0.000837 AC: 1222AN: 1459682Hom.: 2 Cov.: 32 AF XY: 0.000874 AC XY: 635AN XY: 726146
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GnomAD4 genome ? AF: 0.000722 AC: 110AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial acute necrotizing encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | RANBP2: BP4, BP7 - |
Computational scores
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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