XM_047445367.1:c.8371-209360C>T

Variant names:

• chr2-109632044-C-T
• rs2903696
• XM_047445367.1:c.8371-209360C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047445367.1(RANBP2):​c.8371-209360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 152,092 control chromosomes in the GnomAD database, including 628 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.047 (628 hom., cov: 32)
• Consequence: RANBP2 XM_047445367.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 1 publications found

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]

RANBP2 Gene-Disease associations (from GenCC):

• familial acute necrotizing encephalopathy

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7080 AN: 151974 Hom.: 618 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0467 AC: 7102 AN: 152092 Hom.: 628 Cov.: 32 AF XY: 0.0513 AC XY: 3811 AN XY: 74346

African (AFR) AF: 0.0129 AC: 535 AN: 41490

American (AMR) AF: 0.198 AC: 3021 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 179 AN: 3464

East Asian (EAS) AF: 0.238 AC: 1225 AN: 5138

South Asian (SAS) AF: 0.0866 AC: 416 AN: 4804

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0200 AC: 1360 AN: 68012

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0300 Hom.: 37

Bravo AF: 0.0636

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.023

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2903696; hg19: chr2-110389621;