rs61748147

Positions:

chr2-108763494-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006267.5(RANBP2):c.2955G>A(p.Pro985=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00697 in 1,614,010 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0072 ( 88 hom. )

Consequence

RANBP2
NM_006267.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.290

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-108763494-G-A is Benign according to our data. Variant chr2-108763494-G-A is described in ClinVar as [Benign]. Clinvar id is 382463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-108763494-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00501 (763/152188) while in subpopulation SAS AF= 0.0212 (102/4814). AF 95% confidence interval is 0.0179. There are 4 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP2	NM_006267.5 linkuse as main transcript	c.2955G>A	p.Pro985=	synonymous_variant	20/29	ENST00000283195.11	NP_006258.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RANBP2	ENST00000283195.11 linkuse as main transcript	c.2955G>A	p.Pro985=	synonymous_variant	20/29	1	NM_006267.5	ENSP00000283195	P1
RANBP2	ENST00000697737.1 linkuse as main transcript	c.2602+4946G>A		intron_variant				ENSP00000513426
RANBP2	ENST00000697740.1 linkuse as main transcript	c.2524+4946G>A		intron_variant				ENSP00000513427

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

762

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00801

AC:

2010

AN:

251066

Hom.:

AF XY:

0.00828

AC XY:

1124

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.0266

Gnomad SAS exome

AF:

0.0200

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00537

Gnomad OTH exome

AF:

0.00801

GnomAD4 exome

AF:

0.00718

AC:

10493

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

5457

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00479

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.000711

Gnomad4 NFE exome

AF:

0.00589

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.00501

AC:

763

AN:

152188

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

398

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00635

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.00504

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 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

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.9

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over