rs2294305

Variant names:

• chr20-7888809-T-C
• rs2294305
• NM_017545.3:c.814-2945A>G

Variant summary

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

The NM_017545.3(HAO1):​c.814-2945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,156 control chromosomes in the GnomAD database, including 1,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.078 (1054 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -4.65
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.814-2945A>G		intron_variant	Intron 5 of 7	ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.814-2945A>G		intron_variant	Intron 5 of 7	1	NM_017545.3	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11876 AN: 152036 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0648

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

GnomAD4 genome AF: 0.0782 AC: 11895 AN: 152156 Hom.: 1054 Cov.: 32 AF XY: 0.0814 AC XY: 6053 AN XY: 74384

African (AFR) AF: 0.148 AC: 6129 AN: 41490

American (AMR) AF: 0.102 AC: 1554 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2165 AN: 5160

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4826

European-Finnish (FIN) AF: 0.0270 AC: 286 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0188 AC: 1280 AN: 68004

Other (OTH) AF: 0.0651 AC: 137 AN: 2106

Alfa AF: 0.0448 Hom.: 65

Bravo AF: 0.0888

Asia WGS AF: 0.209 AC: 726 AN: 3476

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	-0.97
CADD	Benign	0.0030
DANN	Benign	0.50
PhyloP100		-4.6
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: rs2294305; hg19: chr20-7869456;