22-20260335-T-C

Variant names:

• chr22-20260335-T-C
• rs854927
• NM_023004.6:c.22+7736A>G

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+7736A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 152,246 control chromosomes in the GnomAD database, including 73,628 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 0.98 (73628 hom., cov: 33)
• Consequence: RTN4R NM_023004.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4R	NM_023004.6	c.22+7736A>G		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+7736A>G		intron_variant	Intron 1 of 1	1	NM_023004.6	ENSP00000043402.7

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149570 AN: 152128 Hom.: 73581 Cov.: 33

Gnomad AFR AF: 0.941

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

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

GnomAD4 genome AF: 0.983 AC: 149675 AN: 152246 Hom.: 73628 Cov.: 33 AF XY: 0.984 AC XY: 73245 AN XY: 74448

African (AFR) AF: 0.941 AC: 39093 AN: 41530

American (AMR) AF: 0.994 AC: 15219 AN: 15308

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5160

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67992 AN: 68006

Other (OTH) AF: 0.988 AC: 2087 AN: 2112

Alfa AF: 0.989 Hom.: 9252

Bravo AF: 0.981

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.54
PhyloP100		-2.4
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: rs854927; hg19: chr22-20247858;