rs2968804

Positions:

• chr2-54977362-G-C
• chr2-54977362-G-T

Variant summary

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

The NM_020532.5(RTN4):​c.3361-2598C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,216 control chromosomes in the GnomAD database, including 35,524 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 0.68 (35524 hom., cov: 29)
• Consequence: RTN4 NM_020532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN4	NM_020532.5	c.3361-2598C>G		intron_variant		ENST00000337526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4	ENST00000337526.11	c.3361-2598C>G		intron_variant		1	NM_020532.5

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103494 AN: 151118 Hom.: 35501 Cov.: 29

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.685 AC: 103556 AN: 151216 Hom.: 35524 Cov.: 29 AF XY: 0.679 AC XY: 50107 AN XY: 73796

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.697

Alfa AF: 0.586 Hom.: 1617

Bravo AF: 0.682

Asia WGS AF: 0.603 AC: 2097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.66

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: rs2968804; hg19: chr2-55204498;