1-119375480-C-G

Variant names:

• chr1-119375480-C-G
• rs10494225
• NM_016527.4:c.-8-5598C>G

Variant summary

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

The NM_016527.4(HAO2):​c.-8-5598C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,978 control chromosomes in the GnomAD database, including 1,920 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 0.13 (1920 hom., cov: 32)
• Consequence: HAO2 NM_016527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 4 publications found

Genes affected

HAO2 (HGNC:4810): (hydroxyacid oxidase 2) This gene is one of three related genes that have 2-hydroxyacid oxidase activity. The encoded protein localizes to the peroxisome has the highest activity toward the substrate 2-hydroxypalmitate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ENSG00000227712 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	NM_016527.4	MANE Select	c.-8-5598C>G		intron	N/A	NP_057611.1
	HAO2	NM_001005783.3		c.-189-5024C>G		intron	N/A	NP_001005783.2
	HAO2	NM_001377472.1		c.-189-5024C>G		intron	N/A	NP_001364401.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	ENST00000325945.4	TSL:1 MANE Select	c.-8-5598C>G		intron	N/A	ENSP00000316339.3
	HAO2	ENST00000361035.8	TSL:1	c.-189-5024C>G		intron	N/A	ENSP00000354314.4
	HAO2	ENST00000622548.4	TSL:1	c.-228-5024C>G		intron	N/A	ENSP00000483507.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19971 AN: 151862 Hom.: 1912 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.132 AC: 20013 AN: 151978 Hom.: 1920 Cov.: 32 AF XY: 0.131 AC XY: 9760 AN XY: 74294

African (AFR) AF: 0.272 AC: 11267 AN: 41428

American (AMR) AF: 0.127 AC: 1934 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.0569 AC: 294 AN: 5166

South Asian (SAS) AF: 0.106 AC: 512 AN: 4822

European-Finnish (FIN) AF: 0.0324 AC: 341 AN: 10530

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0744 AC: 5056 AN: 67982

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.107 Hom.: 180

Bravo AF: 0.144

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.65
PhyloP100		-0.46
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: rs10494225; hg19: chr1-119918103;