rs2035515

Variant names:

• chr8-106744433-A-G
• rs2035515
• NM_001198533.2:c.2413-1356A>G

Variant summary

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

The NM_001198533.2(OXR1):​c.2413-1356A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,218 control chromosomes in the GnomAD database, including 1,796 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 0.14 (1796 hom., cov: 33)
• Consequence: OXR1 NM_001198533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 4 publications found

Genes affected

OXR1 (HGNC:15822): (oxidation resistance 1) Predicted to enable oxidoreductase activity. Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within several processes, including adult walking behavior; negative regulation of neuron death; and negative regulation of peptidyl-cysteine S-nitrosylation. Predicted to be located in mitochondrion and nucleolus. Predicted to be active in nucleus. Implicated in cerebellar hyplasia/atrophy, epilepsy, and global developmental delay. [provided by Alliance of Genome Resources, Apr 2022]

OXR1 Gene-Disease associations (from GenCC):

• isolated cerebellar hypoplasia/agenesis

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, G2P

ENSG00000295337 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXR1	NM_001198533.2	c.2413-1356A>G		intron_variant	Intron 15 of 16	ENST00000517566.7	NP_001185462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXR1	ENST00000517566.7	c.2413-1356A>G		intron_variant	Intron 15 of 16	1	NM_001198533.2	ENSP00000429205.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21175 AN: 152100 Hom.: 1793 Cov.: 33

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.139 AC: 21192 AN: 152218 Hom.: 1796 Cov.: 33 AF XY: 0.142 AC XY: 10601 AN XY: 74424

African (AFR) AF: 0.0757 AC: 3146 AN: 41548

American (AMR) AF: 0.182 AC: 2780 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5176

South Asian (SAS) AF: 0.209 AC: 1009 AN: 4820

European-Finnish (FIN) AF: 0.127 AC: 1353 AN: 10618

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9607 AN: 68008

Other (OTH) AF: 0.144 AC: 304 AN: 2110

Alfa AF: 0.140 Hom.: 270

Bravo AF: 0.144

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.49
PhyloP100		0.10
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: rs2035515; hg19: chr8-107756661;