Variant 14-59745908-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021136.3(RTN1):c.815G>A(p.Arg272His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,960 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 32 hom. )

Consequence

RTN1
NM_021136.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.111

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024955273).

BP6

Variant 14-59745908-C-T is Benign according to our data. Variant chr14-59745908-C-T is described in ClinVar as [Benign]. Clinvar id is 708579.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1761/152170) while in subpopulation AFR AF= 0.0403 (1673/41508). AF 95% confidence interval is 0.0387. There are 31 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RTN1	NM_021136.3 linkuse as main transcript	c.815G>A	p.Arg272His	missense_variant	2/9	ENST00000267484.10
RTN1	XM_011537063.4 linkuse as main transcript	c.815G>A	p.Arg272His	missense_variant	2/4
RTN1	XM_047431674.1 linkuse as main transcript	c.815G>A	p.Arg272His	missense_variant	2/4
RTN1	XR_007064042.1 linkuse as main transcript	n.961G>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN1	ENST00000267484.10 linkuse as main transcript	c.815G>A	p.Arg272His	missense_variant	2/9	1	NM_021136.3		Q16799-1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1759

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00304

AC:

764

AN:

251154

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0421

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00115

AC:

1687

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

670

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.0116

AC:

1761

AN:

152170

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

790

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0403

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.0132

ESP6500AA

AF:

0.0397

AC:

175

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00365

AC:

443

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.026

DANN

Benign

0.25

DEOGEN2

Benign

0.0035

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.027

Sift

Benign

0.86

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.0

B;.

Vest4

0.12

MVP

0.043

MPC

0.13

ClinPred

0.0061

GERP RS

-4.0

Varity_R

0.018

gMVP

0.090

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