rs2142697

Variant names:

• chr20-7926296-G-A
• rs2142697
• NM_017545.3:c.289+8188C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-7926296-G-A
• chr20-7926296-G-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+8188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,874 control chromosomes in the GnomAD database, including 8,932 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 (8932 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.103
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.289+8188C>T		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+8188C>T		intron_variant	Intron 2 of 7	1	NM_017545.3	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47567 AN: 151754 Hom.: 8916 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.314 AC: 47640 AN: 151874 Hom.: 8932 Cov.: 32 AF XY: 0.313 AC XY: 23256 AN XY: 74242

African (AFR) AF: 0.507 AC: 20977 AN: 41410

American (AMR) AF: 0.197 AC: 2996 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3466

East Asian (EAS) AF: 0.511 AC: 2635 AN: 5158

South Asian (SAS) AF: 0.500 AC: 2406 AN: 4810

European-Finnish (FIN) AF: 0.157 AC: 1659 AN: 10554

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

European-Non Finnish (NFE) AF: 0.219 AC: 14867 AN: 67914

Other (OTH) AF: 0.310 AC: 654 AN: 2112

Alfa AF: 0.220 Hom.: 890

Bravo AF: 0.319

Asia WGS AF: 0.520 AC: 1807 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	-0.88
CADD	Benign	2.4
DANN	Benign	0.40
PhyloP100		-0.10
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: rs2142697; hg19: chr20-7906943;