22-20253637-C-T

Variant names:

• chr22-20253637-C-T
• rs1567871
• NM_023004.6:c.23-10527G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023004.6(RTN4R):​c.23-10527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,976 control chromosomes in the GnomAD database, including 4,369 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 0.23 (4369 hom., cov: 32)
• Consequence: RTN4R NM_023004.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 11 publications found

Genes affected

RTN4R (HGNC:18601): (reticulon 4 receptor) This gene encodes the receptor for reticulon 4, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023004.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4R	NM_023004.6	MANE Select	c.23-10527G>A		intron	N/A	NP_075380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4R	ENST00000043402.8	TSL:1 MANE Select	c.23-10527G>A		intron	N/A	ENSP00000043402.7
	RTN4R	ENST00000416372.5	TSL:3	c.80-10527G>A		intron	N/A	ENSP00000396872.1
	RTN4R	ENST00000463936.1	TSL:4	n.368-10527G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35080 AN: 151858 Hom.: 4368 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.231 AC: 35105 AN: 151976 Hom.: 4369 Cov.: 32 AF XY: 0.236 AC XY: 17534 AN XY: 74272

African (AFR) AF: 0.177 AC: 7356 AN: 41480

American (AMR) AF: 0.237 AC: 3622 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3466

East Asian (EAS) AF: 0.404 AC: 2083 AN: 5150

South Asian (SAS) AF: 0.188 AC: 904 AN: 4808

European-Finnish (FIN) AF: 0.370 AC: 3893 AN: 10522

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15872 AN: 67968

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.223 Hom.: 7410

Bravo AF: 0.220

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.50
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1567871; hg19: chr22-20241160;