20-7895116-C-T

Position:

• chr20-7895116-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.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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO1	NM_017545.3	c.813+17G>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.813+17G>A		intron_variant		1	NM_017545.3	ENSP00000368066.3

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

GnomAD3 exomes AF: 0.00822 AC: 2062 AN: 250824 Hom.: 91 AF XY: 0.00583 AC XY: 790 AN XY: 135552

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 SAS exome AF: 0.000458

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

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.00451

Gnomad4 ASJ exome AF: 0.000786

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000630

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.00725

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

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00922 Hom.: 9

Bravo AF: 0.0339

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs8124232; hg19: chr20-7875763;