Variant 14-59727466-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021136.3(RTN1):c.1218G>A(p.Ala406=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,568,242 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

RTN1
NM_021136.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.80

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-59727466-C-T is Benign according to our data. Variant chr14-59727466-C-T is described in ClinVar as [Benign]. Clinvar id is 787944.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.8 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTN1	NM_021136.3 linkuse as main transcript	c.1218G>A	p.Ala406=	synonymous_variant	3/9	ENST00000267484.10	NP_066959.1
RTN1	XM_011537063.4 linkuse as main transcript	c.1218G>A	p.Ala406=	synonymous_variant	3/4		XP_011535365.1
RTN1	XM_047431674.1 linkuse as main transcript	c.1218G>A	p.Ala406=	synonymous_variant	3/4		XP_047287630.1
RTN1	XR_007064042.1 linkuse as main transcript	n.1364G>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10 linkuse as main transcript	c.1218G>A	p.Ala406=	synonymous_variant	3/9	1	NM_021136.3	ENSP00000267484		Q16799-1
RTN1	ENST00000432103.6 linkuse as main transcript	n.248G>A		non_coding_transcript_exon_variant	1/7	1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

387

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00907

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000605

AC:

107

AN:

176840

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

95190

show subpopulations

Gnomad AFR exome

AF:

0.00968

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000750

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000295

AC:

418

AN:

1415916

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

170

AN XY:

700386

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.000419

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000803

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.000681

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152326

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00904

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00958

Hom.:

833

Bravo

AF:

0.00284

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.41

DANN

Benign

0.78

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