11-63681666-C-T

Variant names:

• chr11-63681666-C-T
• rs11551949
• NM_001265589.2:c.30C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001265589.2(RTN3):​c.30C>T​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,611,502 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (92 hom.)
• Consequence: RTN3 NM_001265589.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.269

Genes affected

RTN3 (HGNC:10469): (reticulon 3) This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-63681666-C-T is Benign according to our data. Variant chr11-63681666-C-T is described in ClinVar as [Benign]. Clinvar id is 777228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN3	NM_001265589.2	c.30C>T	p.Ser10Ser	synonymous_variant	Exon 1 of 9	ENST00000377819.10	NP_001252518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN3	ENST00000377819.10	c.30C>T	p.Ser10Ser	synonymous_variant	Exon 1 of 9	1	NM_001265589.2	ENSP00000367050.5

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1180 AN: 152270 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00850

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00786 AC: 1950 AN: 247996 AF XY: 0.00785

Gnomad AFR exome AF: 0.00159

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00572

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00677

GnomAD4 exome AF: 0.00972 AC: 14176 AN: 1459114 Hom.: 92 Cov.: 31 AF XY: 0.00946 AC XY: 6863 AN XY: 725696

Gnomad4 AFR exome AF: 0.00138 AC: 46 AN: 33326

Gnomad4 AMR exome AF: 0.00557 AC: 247 AN: 44382

Gnomad4 ASJ exome AF: 0.0227 AC: 592 AN: 26036

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39536

Gnomad4 SAS exome AF: 0.000674 AC: 58 AN: 86038

Gnomad4 FIN exome AF: 0.00626 AC: 333 AN: 53182

Gnomad4 NFE exome AF: 0.0111 AC: 12345 AN: 1110598

Gnomad4 Remaining exome AF: 0.00901 AC: 543 AN: 60274

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152388 Hom.: 9 Cov.: 32 AF XY: 0.00696 AC XY: 519 AN XY: 74530

Gnomad4 AFR AF: 0.00224 AC: 0.00223558 AN: 0.00223558

Gnomad4 AMR AF: 0.00849 AC: 0.00849118 AN: 0.00849118

Gnomad4 ASJ AF: 0.0230 AC: 0.0230415 AN: 0.0230415

Gnomad4 EAS AF: 0.000193 AC: 0.000192604 AN: 0.000192604

Gnomad4 SAS AF: 0.000414 AC: 0.000413907 AN: 0.000413907

Gnomad4 FIN AF: 0.00508 AC: 0.00507996 AN: 0.00507996

Gnomad4 NFE AF: 0.0117 AC: 0.0117007 AN: 0.0117007

Gnomad4 OTH AF: 0.00992 AC: 0.00992439 AN: 0.00992439

Alfa AF: 0.0101 Hom.: 4

Bravo AF: 0.00739

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11551949; hg19: chr11-63449138;