rs701421

Positions:

• chr22-20258558-T-A
• chr22-20258558-T-C
• chr22-20258558-T-G

Variant summary

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

The NM_023004.6(RTN4R):​c.22+9513A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,086 control chromosomes in the GnomAD database, including 27,125 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 0.58 (27125 hom., cov: 34)
• Consequence: RTN4R NM_023004.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4R	NM_023004.6	c.22+9513A>T		intron_variant		ENST00000043402.8	NP_075380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4R	ENST00000043402.8	c.22+9513A>T		intron_variant		1	NM_023004.6	ENSP00000043402	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88318 AN: 151968 Hom.: 27089 Cov.: 34

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.581 AC: 88405 AN: 152086 Hom.: 27125 Cov.: 34 AF XY: 0.586 AC XY: 43582 AN XY: 74348

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.510

Alfa AF: 0.540 Hom.: 2758

Bravo AF: 0.568

Asia WGS AF: 0.694 AC: 2413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.82

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: rs701421; hg19: chr22-20246081;