rs6077285

Positions:

• chr20-7900243-G-C
• chr20-7900243-G-T

Variant summary

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

The NM_017545.3(HAO1):​c.722-5019C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,970 control chromosomes in the GnomAD database, including 4,880 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 0.23 (4880 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAO1	NM_017545.3	c.722-5019C>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.722-5019C>G		intron_variant		1	NM_017545.3	ENSP00000368066	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35018 AN: 151852 Hom.: 4863 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.231 AC: 35083 AN: 151970 Hom.: 4880 Cov.: 32 AF XY: 0.233 AC XY: 17324 AN XY: 74286

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.256

Alfa AF: 0.178 Hom.: 356

Bravo AF: 0.248

Asia WGS AF: 0.472 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.32

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: rs6077285; hg19: chr20-7880890;