rs11894868

chr2-55002884-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020532.5(RTN4):c.3014-15186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,284 control chromosomes in the GnomAD database, including 65 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 0.027 (65 hom., cov: 32)
• Consequence: RTN4 NM_020532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

RTN4 (HGNC:14085): (reticulon 4) 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. The product of this gene is a potent neurite outgrowth inhibitor which may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.027 (4105/152284) while in subpopulation EAS AF= 0.0497 (258/5194). AF 95% confidence interval is 0.0447. There are 65 homozygotes in gnomad4. There are 1998 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN4	NM_020532.5	c.3014-15186A>G		intron_variant		ENST00000337526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4	ENST00000337526.11	c.3014-15186A>G		intron_variant		1	NM_020532.5

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4103 AN: 152166 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0270 AC: 4105 AN: 152284 Hom.: 65 Cov.: 32 AF XY: 0.0268 AC XY: 1998 AN XY: 74464

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0250

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0242 Hom.: 42

Bravo AF: 0.0255

Asia WGS AF: 0.0360 AC: 126 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.13
Dann	Benign	0.81

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: rs11894868; hg19: chr2-55230020;