20-7910391-A-G

Variant names:

• chr20-7910391-A-G
• rs1983560
• NM_017545.3:c.545+3773T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017545.3(HAO1):​c.545+3773T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,104 control chromosomes in the GnomAD database, including 26,623 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 0.55 (26623 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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.545+3773T>C		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.545+3773T>C		intron	N/A	ENSP00000368066.3	Q9UJM8
	HAO1	ENST00000891783.1		c.545+3773T>C		intron	N/A	ENSP00000561842.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83890 AN: 151986 Hom.: 26563 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.552 AC: 84017 AN: 152104 Hom.: 26623 Cov.: 32 AF XY: 0.554 AC XY: 41188 AN XY: 74350

African (AFR) AF: 0.826 AC: 34304 AN: 41522

American (AMR) AF: 0.549 AC: 8386 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3468

East Asian (EAS) AF: 0.992 AC: 5134 AN: 5178

South Asian (SAS) AF: 0.653 AC: 3146 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10572

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25744 AN: 67960

Other (OTH) AF: 0.559 AC: 1179 AN: 2108

Alfa AF: 0.479 Hom.: 3109

Bravo AF: 0.583

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.88
PhyloP100		0.16
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: rs1983560; hg19: chr20-7891038;