rs10496037

Positions:

• chr2-55030541-C-T

Variant summary

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

The NM_020532.5(RTN4):​c.557-2321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,040 control chromosomes in the GnomAD database, including 2,052 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 0.15 (2052 hom., cov: 32)
• Consequence: RTN4 NM_020532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4	NM_020532.5	c.557-2321G>A		intron_variant		ENST00000337526.11	NP_065393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4	ENST00000337526.11	c.557-2321G>A		intron_variant		1	NM_020532.5	ENSP00000337838

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22894 AN: 151922 Hom.: 2050 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.151 AC: 22912 AN: 152040 Hom.: 2052 Cov.: 32 AF XY: 0.149 AC XY: 11080 AN XY: 74324

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.125

Alfa AF: 0.117 Hom.: 1389

Bravo AF: 0.159

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.3
DANN	Benign	0.69

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: rs10496037; hg19: chr2-55257677;