2-55030541-C-T

Variant names:

• chr2-55030541-C-T
• rs10496037
• NM_020532.5:c.557-2321G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.87).
• 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 rank	MANE	Protein	UniProt
RTN4	NM_020532.5	c.557-2321G>A		intron_variant	Intron 1 of 8	ENST00000337526.11	NP_065393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4	ENST00000337526.11	c.557-2321G>A		intron_variant	Intron 1 of 8	1	NM_020532.5	ENSP00000337838.6

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

African (AFR) AF: 0.257 AC: 10669 AN: 41442

American (AMR) AF: 0.124 AC: 1890 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3466

East Asian (EAS) AF: 0.0813 AC: 421 AN: 5178

South Asian (SAS) AF: 0.0973 AC: 469 AN: 4822

European-Finnish (FIN) AF: 0.0948 AC: 1003 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7528 AN: 67974

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.132 Hom.: 2799

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
PhyloP100		0.12
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: rs10496037; hg19: chr2-55257677;