NM_017545.3:c.289+2189G>C

Variant names:

• chr20-7932295-C-G
• rs2235245
• NM_017545.3:c.289+2189G>C

Variant summary

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

The NM_017545.3(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 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.331
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.289+2189G>C		intron_variant	Intron 2 of 7	ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.289+2189G>C		intron_variant	Intron 2 of 7	1	NM_017545.3	ENSP00000368066.3

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

African (AFR) AF: 0.307 AC: 12746 AN: 41466

American (AMR) AF: 0.339 AC: 5184 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2469 AN: 5146

South Asian (SAS) AF: 0.151 AC: 726 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1854 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12150 AN: 68012

Other (OTH) AF: 0.255 AC: 540 AN: 2114

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

Mar 01, 2014

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

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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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
PhyloP100		-0.33
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: rs2235245; hg19: chr20-7912942;