rs941425

Variant names:

• chr20-7924636-G-A
• rs941425
• NM_017545.3:c.289+9848C>T

Variant summary

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

The NM_017545.3(HAO1):​c.289+9848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,920 control chromosomes in the GnomAD database, including 4,389 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 0.22 (4389 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO1	NM_017545.3	c.289+9848C>T		intron_variant	Intron 2 of 7	ENST00000378789.4	NP_060015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAO1	ENST00000378789.4	c.289+9848C>T		intron_variant	Intron 2 of 7	1	NM_017545.3	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33300 AN: 151802 Hom.: 4380 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.220 AC: 33347 AN: 151920 Hom.: 4389 Cov.: 32 AF XY: 0.216 AC XY: 16044 AN XY: 74242

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.210

Alfa AF: 0.181 Hom.: 1773

Bravo AF: 0.225

Asia WGS AF: 0.205 AC: 712 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.17

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: rs941425; hg19: chr20-7905283;