rs11894868

Variant names:

• chr2-55002884-T-C
• rs11894868
• NM_020532.5:c.3014-15186A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020532.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4	NM_020532.5	MANE Select	c.3014-15186A>G		intron	N/A	NP_065393.1	Q9NQC3-1
	RTN4	NM_001321859.2		c.2396-15186A>G		intron	N/A	NP_001308788.1	Q9NQC3-6
	RTN4	NM_001321860.1		c.2396-15186A>G		intron	N/A	NP_001308789.1	Q9NQC3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4	ENST00000337526.11	TSL:1 MANE Select	c.3014-15186A>G		intron	N/A	ENSP00000337838.6	Q9NQC3-1
	RTN4	ENST00000357376.7	TSL:1	c.2396-15186A>G		intron	N/A	ENSP00000349944.3	Q9NQC3-6
	RTN4	ENST00000394611.6	TSL:1	c.2396-15186A>G		intron	N/A	ENSP00000378109.2	Q9NQC3-6

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

African (AFR) AF: 0.0310 AC: 1290 AN: 41566

American (AMR) AF: 0.0190 AC: 291 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.0497 AC: 258 AN: 5194

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4828

European-Finnish (FIN) AF: 0.0329 AC: 349 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0250 AC: 1700 AN: 68010

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0247 Hom.: 55

Bravo AF: 0.0255

Asia WGS AF: 0.0360 AC: 126 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.81
PhyloP100		-2.6
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

Other links and lift over

dbSNP: rs11894868; hg19: chr2-55230020;