11-63729460-G-T

Variant names:

• chr11-63729460-G-T
• rs1202130
• NM_001265589.2:c.2530+8428G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001265589.2(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 NM_001265589.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265589.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	NM_001265589.2	MANE Select	c.2530+8428G>T		intron	N/A	NP_001252518.1
	RTN3	NM_201428.3		c.2473+8428G>T		intron	N/A	NP_958831.1
	RTN3	NM_001265590.2		c.2194+8428G>T		intron	N/A	NP_001252519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	ENST00000377819.10	TSL:1 MANE Select	c.2530+8428G>T		intron	N/A	ENSP00000367050.5
	RTN3	ENST00000339997.8	TSL:1	c.2473+8428G>T		intron	N/A	ENSP00000344106.4
	RTN3	ENST00000540798.5	TSL:1	c.2194+8428G>T		intron	N/A	ENSP00000442733.1

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

African (AFR) AF: 0.846 AC: 10966 AN: 12968

American (AMR) AF: 0.941 AC: 2621 AN: 2786

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 1576 AN: 1610

East Asian (EAS) AF: 0.942 AC: 1290 AN: 1370

South Asian (SAS) AF: 0.944 AC: 1078 AN: 1142

European-Finnish (FIN) AF: 0.772 AC: 301 AN: 390

Middle Eastern (MID) AF: 0.826 AC: 38 AN: 46

European-Non Finnish (NFE) AF: 0.970 AC: 26947 AN: 27786

Other (OTH) AF: 0.939 AC: 612 AN: 652

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1202130; hg19: chr11-63496932;