20-7925300-T-C

Position:

• chr20-7925300-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000378789.4(HAO1):​c.289+9184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,054 control chromosomes in the GnomAD database, including 27,167 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 0.56 (27167 hom., cov: 33)
• Consequence: HAO1 ENST00000378789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO1	NM_017545.3	c.289+9184A>G		intron_variant		ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.289+9184A>G		intron_variant		1	NM_017545.3	ENSP00000368066	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85259 AN: 151936 Hom.: 27115 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.561 AC: 85375 AN: 152054 Hom.: 27167 Cov.: 33 AF XY: 0.563 AC XY: 41808 AN XY: 74318

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.565

Alfa AF: 0.434 Hom.: 20873

Bravo AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.46

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: rs2423334; hg19: chr20-7905947;