NM_023004.6:c.23-4567C>T

Variant names:

• chr22-20247677-G-A
• rs696880
• NM_023004.6:c.23-4567C>T

Variant summary

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

The NM_023004.6(RTN4R):​c.23-4567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,852 control chromosomes in the GnomAD database, including 28,862 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 0.61 (28862 hom., cov: 31)
• Consequence: RTN4R NM_023004.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4R	NM_023004.6	c.23-4567C>T		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.23-4567C>T		intron_variant	Intron 1 of 1	1	NM_023004.6	ENSP00000043402.7

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92812 AN: 151734 Hom.: 28836 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.612 AC: 92888 AN: 151852 Hom.: 28862 Cov.: 31 AF XY: 0.607 AC XY: 45083 AN XY: 74218

African (AFR) AF: 0.691 AC: 28598 AN: 41380

American (AMR) AF: 0.509 AC: 7775 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3466

East Asian (EAS) AF: 0.464 AC: 2393 AN: 5158

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4814

European-Finnish (FIN) AF: 0.651 AC: 6882 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41162 AN: 67888

Other (OTH) AF: 0.570 AC: 1199 AN: 2104

Alfa AF: 0.596 Hom.: 40167

Bravo AF: 0.602

Asia WGS AF: 0.505 AC: 1754 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	0.11
DANN	Benign	0.19
PhyloP100		-1.3
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: rs696880; hg19: chr22-20235200;