rs2255183

Positions:

• chr20-7939957-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.137+329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,306 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.073 (526 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.267

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAO1	NM_017545.3	c.137+329T>C		intron_variant		ENST00000378789.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAO1	ENST00000378789.4	c.137+329T>C		intron_variant		1	NM_017545.3	P1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11177 AN: 152188 Hom.: 525 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0869

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0734 AC: 11183 AN: 152306 Hom.: 526 Cov.: 32 AF XY: 0.0757 AC XY: 5640 AN XY: 74476

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0765 Hom.: 75

Bravo AF: 0.0687

Asia WGS AF: 0.133 AC: 463 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrolithiasis, calcium oxalate 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	-0.84
CADD	Benign	2.1
DANN	Benign	0.50

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: rs2255183; hg19: chr20-7920604;