rs2423331

Variant names:

• chr20-7920882-A-T
• rs2423331
• NM_017545.3:c.290-6463T>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.290-6463T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,060 control chromosomes in the GnomAD database, including 3,954 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 0.21 (3954 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 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.290-6463T>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.290-6463T>A		intron	N/A	ENSP00000368066.3	Q9UJM8
	HAO1	ENST00000891783.1		c.290-6463T>A		intron	N/A	ENSP00000561842.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31555 AN: 151938 Hom.: 3943 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.208 AC: 31610 AN: 152060 Hom.: 3954 Cov.: 32 AF XY: 0.211 AC XY: 15714 AN XY: 74316

African (AFR) AF: 0.287 AC: 11912 AN: 41468

American (AMR) AF: 0.128 AC: 1962 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2631 AN: 5164

South Asian (SAS) AF: 0.433 AC: 2088 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1381 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10235 AN: 67968

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.174 Hom.: 313

Bravo AF: 0.208

Asia WGS AF: 0.482 AC: 1674 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		0.73
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2423331;

hg19: chr20-7901529;