2-54977362-G-C

Variant names:

• chr2-54977362-G-C
• rs2968804
• NM_020532.5:c.3361-2598C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.8).
• 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 rank	MANE	Protein	UniProt
RTN4	NM_020532.5	c.3361-2598C>G		intron_variant	Intron 5 of 8	ENST00000337526.11	NP_065393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4	ENST00000337526.11	c.3361-2598C>G		intron_variant	Intron 5 of 8	1	NM_020532.5	ENSP00000337838.6

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

African (AFR) AF: 0.669 AC: 27505 AN: 41128

American (AMR) AF: 0.645 AC: 9820 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2152 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3580 AN: 5148

South Asian (SAS) AF: 0.523 AC: 2509 AN: 4798

European-Finnish (FIN) AF: 0.694 AC: 7107 AN: 10240

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.716 AC: 48590 AN: 67894

Other (OTH) AF: 0.697 AC: 1466 AN: 2104

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
PhyloP100		0.15
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: rs2968804; hg19: chr2-55204498;