Variant rs11677099 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020532.5(RTN4):c.1070A>T(p.Asp357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,613,542 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 53 hom., cov: 32)

Exomes 𝑓: 0.024 ( 498 hom. )

Consequence

RTN4
NM_020532.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020200014).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4	NM_020532.5 linkuse as main transcript	c.1070A>T	p.Asp357Val	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.1070A>T	p.Asp357Val	missense_variant	3/9	1	NM_020532.5	ENSP00000337838		Q9NQC3-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2969

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0196

Gnomad FIN

AF:

0.0329

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0224

AC:

5622

AN:

250684

Hom.:

AF XY:

0.0228

AC XY:

3083

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00419

Gnomad AMR exome

AF:

0.00992

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.0541

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.0241

AC:

35189

AN:

1461238

Hom.:

498

Cov.:

AF XY:

0.0241

AC XY:

17545

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00365

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.0567

Gnomad4 SAS exome

AF:

0.0174

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0195

AC:

2968

AN:

152304

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00464

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.0511

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0329

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0169

TwinsUK

AF:

0.0245

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0247

AC:

212

ExAC

AF:

0.0224

AC:

2715

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

EpiCase

AF:

0.0238

EpiControl

AF:

0.0232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

.;.;T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.47

.;.;T;.;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.6

D;D;N;D;D

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.99

.;.;D;.;.

Vest4

0.14

MPC

0.12

ClinPred

0.036

GERP RS

3.9

Varity_R

0.24

gMVP

0.087

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over