11-63729340-T-C

Position:

• chr11-63729340-T-C

Variant summary

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

The NM_001265589.2(RTN3):​c.2530+8308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,748 control chromosomes in the GnomAD database, including 8,040 homozygotes. 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 0.28 (8040 hom., cov: 31)
• Consequence: RTN3 NM_001265589.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN3	NM_001265589.2	c.2530+8308T>C		intron_variant		ENST00000377819.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN3	ENST00000377819.10	c.2530+8308T>C		intron_variant		1	NM_001265589.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42756 AN: 151634 Hom.: 8032 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.282 AC: 42765 AN: 151748 Hom.: 8040 Cov.: 31 AF XY: 0.289 AC XY: 21457 AN XY: 74160

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.321

Alfa AF: 0.321 Hom.: 6919

Bravo AF: 0.288

Asia WGS AF: 0.472 AC: 1638 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.28

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: rs10897445; hg19: chr11-63496812;