rs16994134

Variant names:

• chr20-7913445-T-C
• rs16994134
• NM_017545.3:c.545+719A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-7913445-T-C
• chr20-7913445-T-G

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+719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 152,062 control chromosomes in the GnomAD database, including 460 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 0.063 (460 hom., cov: 32)
• Consequence: HAO1 NM_017545.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO1	NM_017545.3	MANE Select	c.545+719A>G		intron	N/A	NP_060015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO1	ENST00000378789.4	TSL:1 MANE Select	c.545+719A>G		intron	N/A	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9652 AN: 151944 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.0635 AC: 9654 AN: 152062 Hom.: 460 Cov.: 32 AF XY: 0.0673 AC XY: 5004 AN XY: 74346

African (AFR) AF: 0.0149 AC: 619 AN: 41510

American (AMR) AF: 0.142 AC: 2161 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5164

South Asian (SAS) AF: 0.0397 AC: 191 AN: 4814

European-Finnish (FIN) AF: 0.0947 AC: 1002 AN: 10580

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4155 AN: 67978

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0670 Hom.: 639

Bravo AF: 0.0679

Asia WGS AF: 0.114 AC: 398 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94
DANN	Benign	0.48
PhyloP100		-0.86
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: rs16994134; hg19: chr20-7894092;