rs10494225

Positions:

• chr1-119375480-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO2	NM_016527.4	c.-8-5598C>G		intron_variant		ENST00000325945.4	NP_057611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAO2	ENST00000325945.4	c.-8-5598C>G		intron_variant		1	NM_016527.4	ENSP00000316339	P1
HAO2	ENST00000361035.8	c.-189-5024C>G		intron_variant		1		ENSP00000354314
HAO2	ENST00000622548.4	c.-228-5024C>G		intron_variant		1		ENSP00000483507	P1
HAO2	ENST00000457318.5	c.-8-5598C>G		intron_variant		3		ENSP00000393955

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0324

Gnomad4 NFE AF: 0.0744

Gnomad4 OTH AF: 0.125

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494225; hg19: chr1-119918103;