rs9606296

Variant names:

• chr22-20257093-C-T
• rs9606296
• NM_023004.6:c.22+10978G>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.22+10978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,266 control chromosomes in the GnomAD database, including 1,175 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 0.11 (1175 hom., cov: 33)
• Consequence: RTN4R NM_023004.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4R	NM_023004.6	c.22+10978G>A		intron_variant	Intron 1 of 1	ENST00000043402.8	NP_075380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4R	ENST00000043402.8	c.22+10978G>A		intron_variant	Intron 1 of 1	1	NM_023004.6	ENSP00000043402.7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16164 AN: 152148 Hom.: 1179 Cov.: 33

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.106 AC: 16162 AN: 152266 Hom.: 1175 Cov.: 33 AF XY: 0.109 AC XY: 8116 AN XY: 74456

African (AFR) AF: 0.0343 AC: 1425 AN: 41558

American (AMR) AF: 0.114 AC: 1743 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5186

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10612

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9309 AN: 68002

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.127 Hom.: 839

Bravo AF: 0.0966

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		1.2
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: rs9606296; hg19: chr22-20244616;