20-7932295-C-G

Position:

• chr20-7932295-C-G

Variant summary

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

The ENST00000378789.4(HAO1):​c.289+2189G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,090 control chromosomes in the GnomAD database, including 4,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.24 (4898 hom., cov: 32)
• Consequence: HAO1 ENST00000378789.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.331

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO1	NM_017545.3	c.289+2189G>C		intron_variant		ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.289+2189G>C		intron_variant		1	NM_017545.3	ENSP00000368066	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36844 AN: 151972 Hom.: 4893 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.242 AC: 36876 AN: 152090 Hom.: 4898 Cov.: 32 AF XY: 0.244 AC XY: 18110 AN XY: 74346

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.255

Alfa AF: 0.0785 Hom.: 78

Bravo AF: 0.265

Asia WGS AF: 0.306 AC: 1064 AN: 3478

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	-0.92
CADD	Benign	2.0
DANN	Benign	0.46

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: rs2235245; hg19: chr20-7912942;