Variant 22-41254367-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002883.4(RANGAP1):c.1201C>G(p.Arg401Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,920 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 60 hom. )

Consequence

RANGAP1
NM_002883.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0370

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017139614).

BP6

Variant 22-41254367-G-C is Benign according to our data. Variant chr22-41254367-G-C is described in ClinVar as [Benign]. Clinvar id is 780659.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANGAP1	NM_002883.4 linkuse as main transcript	c.1201C>G	p.Arg401Gly	missense_variant	11/16	ENST00000356244.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RANGAP1	ENST00000356244.8 linkuse as main transcript	c.1201C>G	p.Arg401Gly	missense_variant	11/16	1	NM_002883.4	P1
RANGAP1	ENST00000405486.5 linkuse as main transcript	c.1201C>G	p.Arg401Gly	missense_variant	12/17	1		P1
RANGAP1	ENST00000455915.6 linkuse as main transcript	c.1201C>G	p.Arg401Gly	missense_variant	10/15	1		P1
RANGAP1	ENST00000705116.1 linkuse as main transcript	c.1201C>G	p.Arg401Gly	missense_variant	11/16			P1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2177

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00395

AC:

983

AN:

248950

Hom.:

AF XY:

0.00281

AC XY:

379

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.0545

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00161

AC:

2357

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1031

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0554

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.0143

AC:

2179

AN:

152080

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1008

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0497

Gnomad4 AMR

AF:

0.00498

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00467

Hom.:

Bravo

AF:

0.0167

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0545

AC:

240

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00479

AC:

581

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.41

Cadd

Benign

3.6

Dann

Benign

0.25

DEOGEN2

Benign

0.26

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.051

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.42

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.089

MVP

0.17

MPC

0.28

ClinPred

0.0024

GERP RS

-8.1

Varity_R

0.034

gMVP

0.091

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