Variant 2-55025218-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020532.5(RTN4):c.2881C>G(p.Gln961Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RTN4
NM_020532.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

RTN4 (HGNC:14085): (reticulon 4) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. The product of this gene is a potent neurite outgrowth inhibitor which may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

RTN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0044970512).

BP6

Variant 2-55025218-G-C is Benign according to our data. Variant chr2-55025218-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 746363.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4	NM_020532.5 linkuse as main transcript	c.2881C>G	p.Gln961Glu	missense_variant	3/9	ENST00000337526.11	NP_065393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4	ENST00000337526.11 linkuse as main transcript	c.2881C>G	p.Gln961Glu	missense_variant	3/9	1	NM_020532.5	ENSP00000337838		Q9NQC3-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000355

AC:

AN:

250598

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1461554

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152250

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00359

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.00129

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.9

DANN

Benign

0.38

DEOGEN2

Benign

0.059

.;.;T;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.58

.;.;T;.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0045

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.24

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;B;.;.

Vest4

0.054

MVP

0.20

MPC

0.030

ClinPred

0.0036

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.055

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