rs10185197

chr2-108783811-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006267.5(RANBP2):c.9585C>T(p.Gly3195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00918 in 1,612,026 control chromosomes in the GnomAD database, including 994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (532 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (462 hom.)
• Consequence: RANBP2 NM_006267.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-108783811-C-T is Benign according to our data. Variant chr2-108783811-C-T is described in ClinVar as [Benign]. Clinvar id is 380107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP2	NM_006267.5	c.9585C>T	p.Gly3195=	synonymous_variant	29/29	ENST00000283195.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP2	ENST00000283195.11	c.9585C>T	p.Gly3195=	synonymous_variant	29/29	1	NM_006267.5	P1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6877 AN: 152062 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.0316

GnomAD3 exomes AF: 0.0127 AC: 3200 AN: 251334 Hom.: 204 AF XY: 0.00968 AC XY: 1315 AN XY: 135850

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00605

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000458

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00750

GnomAD4 exome AF: 0.00540 AC: 7887 AN: 1459846 Hom.: 462 Cov.: 31 AF XY: 0.00478 AC XY: 3472 AN XY: 726394

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.00548

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000759

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0454 AC: 6905 AN: 152180 Hom.: 532 Cov.: 32 AF XY: 0.0438 AC XY: 3261 AN XY: 74392

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00115

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0248 Hom.: 148

Bravo AF: 0.0520

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2016

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	7.8
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10185197; hg19: chr2-109400267;