Genetic Variant RANGAP1:p.Glu364Asp (chr22-41254476-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002883.4(RANGAP1):c.1092G>C(p.Glu364Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RANGAP1
NM_002883.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.643

Publications

0 publications found

Variant links:

Genes affected

RANGAP1 (HGNC:9854): (Ran GTPase activating protein 1) This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RANGAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04086086).

BP6

Variant 22-41254476-C-G is Benign according to our data. Variant chr22-41254476-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2266757.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002883.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANGAP1	NM_002883.4	MANE Select	c.1092G>C	p.Glu364Asp	missense	Exon 11 of 16	NP_002874.1	P46060
RANGAP1	NM_001278651.2		c.1092G>C	p.Glu364Asp	missense	Exon 12 of 17	NP_001265580.1	P46060
RANGAP1	NM_001317930.2		c.1092G>C	p.Glu364Asp	missense	Exon 11 of 16	NP_001304859.1	P46060

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANGAP1	ENST00000356244.8	TSL:1 MANE Select	c.1092G>C	p.Glu364Asp	missense	Exon 11 of 16	ENSP00000348577.3	P46060
RANGAP1	ENST00000405486.5	TSL:1	c.1092G>C	p.Glu364Asp	missense	Exon 12 of 17	ENSP00000385866.1	P46060
RANGAP1	ENST00000455915.6	TSL:1	c.1092G>C	p.Glu364Asp	missense	Exon 10 of 15	ENSP00000401470.2	P46060

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25134

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

83678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46650

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107202

Other (OTH)

AF:

0.00

AC:

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.91

(source)

DANN

Benign

0.071

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.52

M_CAP

Benign

0.0053

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.085

PhyloP100

0.64

PrimateAI

Benign

0.42

PROVEAN

Benign

1.0

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.19

MutPred

0.37

Loss of helix (P = 0.1706)

MVP

0.19

MPC

0.20

ClinPred

0.022

GERP RS

0.76

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.9

Varity_R

0.020

gMVP

0.026

Mutation Taster

=89/11

polymorphism

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over