11-63729460-G-T

Position:

• chr11-63729460-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377819.10(RTN3):​c.2530+8428G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (21555 hom., cov: 7)
• Consequence: RTN3 ENST00000377819.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN3	NM_001265589.2	c.2530+8428G>T		intron_variant		ENST00000377819.10	NP_001252518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN3	ENST00000377819.10	c.2530+8428G>T		intron_variant		1	NM_001265589.2	ENSP00000367050

Frequencies

GnomAD3 genomes AF: 0.932 AC: 45800 AN: 49116 Hom.: 21553 Cov.: 7

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.941

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.932 AC: 45816 AN: 49142 Hom.: 21555 Cov.: 7 AF XY: 0.925 AC XY: 20366 AN XY: 22008

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.43

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: rs1202130; hg19: chr11-63496932;