20-7895116-C-T

Variant names:

• chr20-7895116-C-T
• rs8124232
• NM_017545.3:c.813+17G>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.813+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,507,792 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (227 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (198 hom.)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.813+17G>A		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.813+17G>A		intron	N/A	ENSP00000368066.3	Q9UJM8
	HAO1	ENST00000891783.1		c.813+17G>A		intron	N/A	ENSP00000561842.1

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4525 AN: 152098 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00822 AC: 2062 AN: 250824 AF XY: 0.00583

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.000498

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00325 AC: 4402 AN: 1355576 Hom.: 198 Cov.: 24 AF XY: 0.00278 AC XY: 1895 AN XY: 680462

African (AFR) AF: 0.111 AC: 3498 AN: 31482

American (AMR) AF: 0.00451 AC: 201 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.000786 AC: 20 AN: 25434

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39204

South Asian (SAS) AF: 0.000630 AC: 53 AN: 84066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00774 AC: 43 AN: 5558

European-Non Finnish (NFE) AF: 0.000171 AC: 174 AN: 1015048

Other (OTH) AF: 0.00725 AC: 412 AN: 56866

GnomAD4 genome AF: 0.0299 AC: 4552 AN: 152216 Hom.: 227 Cov.: 32 AF XY: 0.0285 AC XY: 2124 AN XY: 74410

African (AFR) AF: 0.104 AC: 4329 AN: 41512

American (AMR) AF: 0.0101 AC: 154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68010

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0117 Hom.: 25

Bravo AF: 0.0339

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8124232; hg19: chr20-7875763;