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GeneBe

14-59727466-C-T

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.8 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RTN1NM_021136.3 linkuse as main transcriptc.1218G>A p.Ala406= synonymous_variant 3/9 ENST00000267484.10
RTN1XM_011537063.4 linkuse as main transcriptc.1218G>A p.Ala406= synonymous_variant 3/4
RTN1XM_047431674.1 linkuse as main transcriptc.1218G>A p.Ala406= synonymous_variant 3/4
RTN1XR_007064042.1 linkuse as main transcriptn.1364G>A non_coding_transcript_exon_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RTN1ENST00000267484.10 linkuse as main transcriptc.1218G>A p.Ala406= synonymous_variant 3/91 NM_021136.3 Q16799-1
RTN1ENST00000432103.6 linkuse as main transcriptn.248G>A non_coding_transcript_exon_variant 1/71

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00254
AC:
387
AN:
152208
Hom.:
2
Cov.:
32
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.:
0
AF XY:
0.000368
AC XY:
35
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.:
3
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00254
AC:
387
AN:
152326
Hom.:
2
Cov.:
32
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:
1
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 submitterclinical testingInvitaeJul 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.

Other links and lift over

dbSNP: rs115497853; hg19: chr14-60194184; API