20-7912993-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017545.3(HAO1):c.545+1171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,112 control chromosomes in the GnomAD database, including 4,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.22 (4836 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.197

Genes affected

HAO1 (HGNC:4809): (hydroxyacid oxidase 1) This gene is one of three related genes that have 2-hydroxyacid oxidase activity yet differ in encoded protein amino acid sequence, tissue expression and substrate preference. Subcellular location of the encoded protein is the peroxisome. Specifically, this gene is expressed primarily in liver and pancreas and the encoded protein is most active on glycolate, a two-carbon substrate. The protein is also active on 2-hydroxy fatty acids. The transcript detected at high levels in pancreas may represent an alternatively spliced form or the use of a multiple near-consensus upstream polyadenylation site. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAO1	NM_017545.3	c.545+1171T>C		intron_variant		ENST00000378789.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAO1	ENST00000378789.4	c.545+1171T>C		intron_variant		1	NM_017545.3	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34131 AN: 151992 Hom.: 4824 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.225 AC: 34188 AN: 152112 Hom.: 4836 Cov.: 32 AF XY: 0.228 AC XY: 16981 AN XY: 74368

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.221

Alfa AF: 0.167 Hom.: 1862

Bravo AF: 0.227

Asia WGS AF: 0.498 AC: 1730 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Calcium oxalate urolithiasis Other:1

association, no assertion criteria provided

case-control

Division of Molecular Genetics and Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University

Mar 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.7
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2423326; hg19: chr20-7893640;