Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006267.5(RANBP2):c.8253G>A(p.Glu2751Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,613,836 control chromosomes in the GnomAD database, including 803,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74410 hom., cov: 33)

Exomes 𝑓: 1.0 ( 728956 hom. )

Consequence

RANBP2
NM_006267.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

Publications

18 publications found

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 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

RANBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-108773007-G-A is Benign according to our data. Variant chr2-108773007-G-A is described in ClinVar as Benign. ClinVar VariationId is 1169866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006267.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RANBP2	NM_006267.5	MANE Select	c.8253G>A	p.Glu2751Glu	synonymous	Exon 23 of 29	NP_006258.3
RANBP2	NM_001415871.1		c.8331G>A	p.Glu2777Glu	synonymous	Exon 24 of 30	NP_001402800.1
RANBP2	NM_001415873.1		c.8253G>A	p.Glu2751Glu	synonymous	Exon 23 of 29	NP_001402802.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RANBP2	ENST00000283195.11	TSL:1 MANE Select	c.8253G>A	p.Glu2751Glu	synonymous	Exon 23 of 29	ENSP00000283195.6
RANBP2	ENST00000697745.1		c.3117G>A	p.Glu1039Glu	synonymous	Exon 4 of 10	ENSP00000513429.1
RANBP2	ENST00000697737.1		c.3006G>A	p.Glu1002Glu	synonymous	Exon 21 of 27	ENSP00000513426.1

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150424

AN:

152226

Hom.:

74351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.991

GnomAD2 exomes

AF:

0.997

AC:

250047

AN:

250850

AF XY:

0.998

show subpopulations

Gnomad AFR exome

AF:

0.957

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1459656

AN:

1461492

Hom.:

728956

Cov.:

AF XY:

0.999

AC XY:

726249

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.958

AC:

32071

AN:

33474

American (AMR)

AF:

0.998

AC:

44599

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26120

AN:

26120

East Asian (EAS)

AF:

1.00

AC:

39670

AN:

39670

South Asian (SAS)

AF:

1.00

AC:

86167

AN:

86172

European-Finnish (FIN)

AF:

1.00

AC:

53404

AN:

53404

Middle Eastern (MID)

AF:

0.999

AC:

5760

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111653

AN:

1111804

Other (OTH)

AF:

0.997

AC:

60212

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

185

278

370

463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.988

AC:

150542

AN:

152344

Hom.:

74410

Cov.:

AF XY:

0.989

AC XY:

73674

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.959

AC:

39861

AN:

41576

American (AMR)

AF:

0.996

AC:

15241

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5185

AN:

5186

South Asian (SAS)

AF:

1.00

AC:

4830

AN:

4830

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68032

AN:

68042

Other (OTH)

AF:

0.991

AC:

2098

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.994

Hom.:

49748

Bravo

AF:

0.986

Asia WGS

AF:

0.998

AC:

3469

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial acute necrotizing encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

3.9

(source)

DANN

Benign

0.47

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs826580

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over