20-7919281-T-C

Variant names:

• chr20-7919281-T-C
• rs2205818
• NM_017545.3:c.290-4862A>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.290-4862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,200 control chromosomes in the GnomAD database, including 5,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.25 (5460 hom., cov: 33)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.02
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017545.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO1	NM_017545.3	MANE Select	c.290-4862A>G		intron	N/A	NP_060015.1	Q9UJM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO1	ENST00000378789.4	TSL:1 MANE Select	c.290-4862A>G		intron	N/A	ENSP00000368066.3	Q9UJM8
	HAO1	ENST00000891783.1		c.290-4862A>G		intron	N/A	ENSP00000561842.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38471 AN: 152082 Hom.: 5454 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.253 AC: 38513 AN: 152200 Hom.: 5460 Cov.: 33 AF XY: 0.254 AC XY: 18906 AN XY: 74404

African (AFR) AF: 0.344 AC: 14266 AN: 41528

American (AMR) AF: 0.343 AC: 5245 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3472

East Asian (EAS) AF: 0.479 AC: 2478 AN: 5170

South Asian (SAS) AF: 0.151 AC: 728 AN: 4826

European-Finnish (FIN) AF: 0.175 AC: 1856 AN: 10604

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12180 AN: 68012

Other (OTH) AF: 0.261 AC: 552 AN: 2116

Alfa AF: 0.237 Hom.: 776

Bravo AF: 0.278

Asia WGS AF: 0.307 AC: 1069 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Nephrolithiasis, calcium oxalate (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.58
PhyloP100		-1.0
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: rs2205818; hg19: chr20-7899928;