XM_047445367.1:c.8371-324802C>T

Variant names:

• chr2-109516602-C-T
• rs11692886
• XM_047445367.1:c.8371-324802C>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.8371-324802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,168 control chromosomes in the GnomAD database, including 4,141 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 0.22 (4141 hom., cov: 33)
• Consequence: RANBP2 XM_047445367.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 4 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=-1.1).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP2	XM_047445367.1	c.8371-324802C>T		intron_variant	Intron 24 of 24		XP_047301323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32861 AN: 152050 Hom.: 4143 Cov.: 33

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.216 AC: 32856 AN: 152168 Hom.: 4141 Cov.: 33 AF XY: 0.214 AC XY: 15884 AN XY: 74394

African (AFR) AF: 0.0928 AC: 3854 AN: 41522

American (AMR) AF: 0.210 AC: 3215 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3466

East Asian (EAS) AF: 0.152 AC: 787 AN: 5164

South Asian (SAS) AF: 0.260 AC: 1254 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2693 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19316 AN: 67982

Other (OTH) AF: 0.229 AC: 484 AN: 2112

Alfa AF: 0.246 Hom.: 799

Bravo AF: 0.209

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs11692886; hg19: chr2-110274179;