8-106686738-A-G

Variant names:

• chr8-106686738-A-G
• rs776965
• NM_001198533.2:c.525+2379A>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.525+2379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,052 control chromosomes in the GnomAD database, including 28,804 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 (28804 hom., cov: 32)
• Consequence: OXR1 NM_001198533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 5 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, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198533.2. 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
	OXR1	NM_001198533.2	MANE Select	c.525+2379A>G		intron	N/A	NP_001185462.1	Q8N573-8
	OXR1	NM_001198532.1		c.528+2379A>G		intron	N/A	NP_001185461.1	Q8N573-1
	OXR1	NM_018002.3		c.525+2379A>G		intron	N/A	NP_060472.2	Q8N573-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXR1	ENST00000517566.7	TSL:1 MANE Select	c.525+2379A>G		intron	N/A	ENSP00000429205.2	Q8N573-8
	OXR1	ENST00000312046.10	TSL:1	c.504+2379A>G		intron	N/A	ENSP00000311026.6	Q8N573-2
	OXR1	ENST00000438229.6	TSL:1	n.*281+2379A>G		intron	N/A	ENSP00000414992.2	E5RFD1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92060 AN: 151936 Hom.: 28760 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.606 AC: 92166 AN: 152052 Hom.: 28804 Cov.: 32 AF XY: 0.600 AC XY: 44578 AN XY: 74326

African (AFR) AF: 0.763 AC: 31674 AN: 41486

American (AMR) AF: 0.514 AC: 7845 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3382 AN: 5166

South Asian (SAS) AF: 0.535 AC: 2582 AN: 4824

European-Finnish (FIN) AF: 0.454 AC: 4791 AN: 10558

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37859 AN: 67970

Other (OTH) AF: 0.589 AC: 1240 AN: 2104

Alfa AF: 0.565 Hom.: 13618

Bravo AF: 0.619

Asia WGS AF: 0.657 AC: 2275 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.11
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: rs776965; hg19: chr8-107698966;