Variant 14-59727615-T-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_021136.3(RTN1):c.1069A>G(p.Ile357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,612,624 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.015 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 65 hom. )

Consequence

RTN1
NM_021136.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

RTN1 (HGNC:10467): (reticulon 1) 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. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

RTN1 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=0.0021155477).

BP6

Variant 14-59727615-T-C is Benign according to our data. Variant chr14-59727615-T-C is described in ClinVar as [Benign]. Clinvar id is 781130.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RTN1	NM_021136.3 linkuse as main transcript	c.1069A>G	p.Ile357Val	missense_variant	3/9	ENST00000267484.10
RTN1	XM_011537063.4 linkuse as main transcript	c.1069A>G	p.Ile357Val	missense_variant	3/4
RTN1	XM_047431674.1 linkuse as main transcript	c.1069A>G	p.Ile357Val	missense_variant	3/4
RTN1	XR_007064042.1 linkuse as main transcript	n.1215A>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN1	ENST00000267484.10 linkuse as main transcript	c.1069A>G	p.Ile357Val	missense_variant	3/9	1	NM_021136.3		Q16799-1
RTN1	ENST00000432103.6 linkuse as main transcript	n.99A>G		non_coding_transcript_exon_variant	1/7	1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2294

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00397

AC:

984

AN:

247898

Hom.:

AF XY:

0.00310

AC XY:

418

AN XY:

134666

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00158

AC:

2307

AN:

1460380

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

988

AN XY:

726486

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000963

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.0152

AC:

2309

AN:

152244

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1099

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.0174

ESP6500AA

AF:

0.0525

AC:

231

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00485

AC:

589

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.95

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.28

N;.

REVEL

Benign

0.060

Sift

Benign

0.14

T;.

Sift4G

Benign

0.46

T;T

Polyphen

0.067

B;.

Vest4

0.24

MVP

0.068

MPC

0.086

ClinPred

0.0060

GERP RS

3.2

Varity_R

0.048

gMVP

0.18

Splicing

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