rs6118004

Variant names:

• chr20-7916402-C-T
• rs6118004
• NM_017545.3:c.290-1983G>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.290-1983G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,126 control chromosomes in the GnomAD database, including 8,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.31 (8979 hom., cov: 33)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -4.49
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.290-1983G>A		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.290-1983G>A		intron_variant	Intron 2 of 7	1	NM_017545.3	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47590 AN: 152008 Hom.: 8963 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.313 AC: 47662 AN: 152126 Hom.: 8979 Cov.: 33 AF XY: 0.313 AC XY: 23296 AN XY: 74394

African (AFR) AF: 0.511 AC: 21193 AN: 41488

American (AMR) AF: 0.198 AC: 3021 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2647 AN: 5182

South Asian (SAS) AF: 0.497 AC: 2399 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1662 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14674 AN: 67986

Other (OTH) AF: 0.308 AC: 651 AN: 2112

Alfa AF: 0.252 Hom.: 14015

Bravo AF: 0.319

Asia WGS AF: 0.522 AC: 1813 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	-1.0
CADD	Benign	0.013
DANN	Benign	0.20
PhyloP100		-4.5
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: rs6118004; hg19: chr20-7897049;