chr11-57460884-C-T

Variant names:

• chr11-57460884-C-T
• rs111949084
• NM_178570.3:c.19C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_178570.3(RTN4RL2):​c.19C>T​(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,406,832 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (3 hom.)
• Consequence: RTN4RL2 NM_178570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 1 publications found

Genes affected

RTN4RL2 (HGNC:23053): (reticulon 4 receptor like 2) Enables signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; corpus callosum development; and negative regulation of neuron projection development. Located in cell surface. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015383929).
• BS2: High AC in GnomAd4 at 117 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4RL2	NM_178570.3	MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	NP_848665.1	Q86UN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4RL2	ENST00000335099.8	TSL:1 MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000335397.3	Q86UN3-1
	RTN4RL2	ENST00000395120.2	TSL:1	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000378552.2	Q86UN3-2
	RTN4RL2	ENST00000533205.5	TSL:3	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000435606.1	G3V1D7

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 152066 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000106 AC: 9 AN: 84972 AF XY: 0.0000837

Gnomad AFR exome AF: 0.00242

Gnomad AMR exome AF: 0.000176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000638

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000113 AC: 142 AN: 1254654 Hom.: 3 Cov.: 29 AF XY: 0.0000862 AC XY: 53 AN XY: 614924

African (AFR) AF: 0.00381 AC: 98 AN: 25724

American (AMR) AF: 0.000139 AC: 3 AN: 21512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21326

East Asian (EAS) AF: 0.00 AC: 0 AN: 27536

South Asian (SAS) AF: 0.0000485 AC: 3 AN: 61796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44290

Middle Eastern (MID) AF: 0.000544 AC: 2 AN: 3678

European-Non Finnish (NFE) AF: 0.0000130 AC: 13 AN: 998622

Other (OTH) AF: 0.000458 AC: 23 AN: 50170

GnomAD4 genome AF: 0.000769 AC: 117 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.000793 AC XY: 59 AN XY: 74414

African (AFR) AF: 0.00262 AC: 109 AN: 41548

American (AMR) AF: 0.000261 AC: 4 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67954

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000375 Hom.: 0

Bravo AF: 0.000941

ExAC AF: 0.000101 AC: 8

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.18	T
Polyphen		0.66	P
Vest4		0.13
MVP		0.41
MPC		2.2
ClinPred		0.063	T
GERP RS		3.0
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.28
gMVP		0.70
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs111949084; hg19: chr11-57228357;