8-106505310-C-T

Variant names:

• chr8-106505310-C-T
• rs1789982
• NM_001198533.2:c.24-13633C>T

Variant summary

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

The NM_001198533.2(OXR1):​c.24-13633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,170 control chromosomes in the GnomAD database, including 54,062 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 0.84 (54062 hom., cov: 32)
• Consequence: OXR1 NM_001198533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXR1	NM_001198533.2	c.24-13633C>T		intron_variant	Intron 2 of 16	ENST00000517566.7	NP_001185462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXR1	ENST00000517566.7	c.24-13633C>T		intron_variant	Intron 2 of 16	1	NM_001198533.2	ENSP00000429205.2
OXR1	ENST00000442977.6	c.27-13633C>T		intron_variant	Intron 1 of 15	2		ENSP00000405424.2
OXR1	ENST00000531443.6	c.24-13633C>T		intron_variant	Intron 2 of 15	5		ENSP00000431966.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127832 AN: 152052 Hom.: 54020 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.841 AC: 127923 AN: 152170 Hom.: 54062 Cov.: 32 AF XY: 0.835 AC XY: 62153 AN XY: 74410

African (AFR) AF: 0.902 AC: 37452 AN: 41530

American (AMR) AF: 0.878 AC: 13430 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3273 AN: 5178

South Asian (SAS) AF: 0.680 AC: 3276 AN: 4818

European-Finnish (FIN) AF: 0.779 AC: 8233 AN: 10570

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56501 AN: 67996

Other (OTH) AF: 0.819 AC: 1729 AN: 2112

Alfa AF: 0.831 Hom.: 30804

Bravo AF: 0.854

Asia WGS AF: 0.683 AC: 2378 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.18
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1789982; hg19: chr8-107517538;