rs587779756

Variant names:

• chr20-7890075-C-T
• rs2235250
• NM_017545.3:c.814-4211G>A

Variant summary

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

The NM_017545.3(HAO1):​c.814-4211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,170 control chromosomes in the GnomAD database, including 1,037 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 (1037 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.441
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.814-4211G>A		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.814-4211G>A		intron_variant	Intron 5 of 7	1	NM_017545.3	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11848 AN: 152050 Hom.: 1037 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0780 AC: 11866 AN: 152170 Hom.: 1037 Cov.: 32 AF XY: 0.0810 AC XY: 6025 AN XY: 74394

African (AFR) AF: 0.149 AC: 6184 AN: 41510

American (AMR) AF: 0.101 AC: 1545 AN: 15272

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

East Asian (EAS) AF: 0.406 AC: 2096 AN: 5164

South Asian (SAS) AF: 0.0569 AC: 275 AN: 4830

European-Finnish (FIN) AF: 0.0269 AC: 285 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0188 AC: 1276 AN: 68012

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

Alfa AF: 0.0546 Hom.: 96

Bravo AF: 0.0885

Asia WGS AF: 0.206 AC: 717 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	-0.85
CADD	Benign	3.1
DANN	Benign	0.40
PhyloP100		-0.44
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: rs2235250; hg19: chr20-7870722;