rs1022208001

Variant names:

• chr11-57476739-C-A
• rs1022208001
• NM_178570.3:c.1091C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-57476739-C-A
• chr11-57476739-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178570.3(RTN4RL2):​c.1091C>A​(p.Ala364Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000772 in 1,295,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A364V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: RTN4RL2 NM_178570.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 0 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]

ENSG00000255301 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20222658).

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.1091C>A	p.Ala364Glu	missense	Exon 3 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.1091C>A	p.Ala364Glu	missense	Exon 3 of 3	ENSP00000335397.3	Q86UN3-1
	ENSG00000255301	ENST00000528885.1	TSL:2	n.539-101G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.72e-7 AC: 1 AN: 1295590 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 633992

African (AFR) AF: 0.00 AC: 0 AN: 25986

American (AMR) AF: 0.00 AC: 0 AN: 21764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18434

East Asian (EAS) AF: 0.00 AC: 0 AN: 31250

South Asian (SAS) AF: 0.00 AC: 0 AN: 64404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 9.62e-7 AC: 1 AN: 1039706

Other (OTH) AF: 0.00 AC: 0 AN: 53326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.84
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.17
Sift	Benign	0.78	T
Sift4G	Benign	0.69	T
Polyphen		0.96	D
Vest4		0.20
MutPred		0.21		Gain of loop (P = 0.0502)
MVP		0.65
MPC		1.8
ClinPred		0.51	D
GERP RS		2.4
Varity_R		0.22
gMVP		0.36
Mutation Taster		=76/24	polymorphism

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: rs1022208001; hg19: chr11-57244212;