20-7901459-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.721+4695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 152,104 control chromosomes in the GnomAD database, including 854 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 0.066 (854 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAO1	NM_017545.3	c.721+4695G>A		intron_variant		ENST00000378789.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAO1	ENST00000378789.4	c.721+4695G>A		intron_variant		1	NM_017545.3	P1

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10001 AN: 151986 Hom.: 852 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0556

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

GnomAD4 genome AF: 0.0659 AC: 10026 AN: 152104 Hom.: 854 Cov.: 32 AF XY: 0.0674 AC XY: 5010 AN XY: 74344

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.0616

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0384 Hom.: 38

Bravo AF: 0.0704

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.8
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2223276; hg19: chr20-7882106;