rs6118004

Positions:

• chr20-7916402-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
HAO1	NM_017545.3	c.290-1983G>A		intron_variant		ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.290-1983G>A		intron_variant		1	NM_017545.3	ENSP00000368066	P1

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

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.308

Alfa AF: 0.235 Hom.: 7588

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.20

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: rs6118004; hg19: chr20-7897049;