chr20-7928519-G-A

Variant names:

• chr20-7928519-G-A
• rs6140463
• NM_017545.3:c.289+5965C>T

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+5965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 147,138 control chromosomes in the GnomAD database, including 5,070 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 (5070 hom., cov: 28)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.353
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 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.289+5965C>T		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.289+5965C>T		intron	N/A	ENSP00000368066.3	Q9UJM8
	HAO1	ENST00000891783.1		c.289+5965C>T		intron	N/A	ENSP00000561842.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 36714 AN: 147056 Hom.: 5071 Cov.: 28

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.250 AC: 36736 AN: 147138 Hom.: 5070 Cov.: 28 AF XY: 0.252 AC XY: 18006 AN XY: 71444

African (AFR) AF: 0.327 AC: 13057 AN: 39912

American (AMR) AF: 0.346 AC: 5110 AN: 14776

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 939 AN: 3448

East Asian (EAS) AF: 0.482 AC: 2448 AN: 5074

South Asian (SAS) AF: 0.152 AC: 708 AN: 4672

European-Finnish (FIN) AF: 0.183 AC: 1646 AN: 8982

Middle Eastern (MID) AF: 0.284 AC: 80 AN: 282

European-Non Finnish (NFE) AF: 0.180 AC: 12044 AN: 67044

Other (OTH) AF: 0.256 AC: 524 AN: 2044

Alfa AF: 0.220 Hom.: 1446

Bravo AF: 0.271

ClinVar

ClinVar submissions

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	-0.87
CADD	Benign	6.3
DANN	Benign	0.58
PhyloP100		-0.35
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: rs6140463; hg19: chr20-7909166;