chr20-7939957-A-G

Variant names:

• chr20-7939957-A-G
• rs2255183
• NM_017545.3:c.137+329T>C

Variant summary

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

The ENST00000378789.4(HAO1):​c.137+329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,306 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.073 (526 hom., cov: 32)
• Consequence: HAO1 ENST00000378789.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.267
• Publications: 4 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=-0.84).
• 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: ENST00000378789.4. 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.137+329T>C		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.137+329T>C		intron	N/A	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11177 AN: 152188 Hom.: 525 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0869

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0734 AC: 11183 AN: 152306 Hom.: 526 Cov.: 32 AF XY: 0.0757 AC XY: 5640 AN XY: 74476

African (AFR) AF: 0.0247 AC: 1028 AN: 41586

American (AMR) AF: 0.0615 AC: 941 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1033 AN: 5180

South Asian (SAS) AF: 0.112 AC: 540 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1139 AN: 10608

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5916 AN: 68022

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0765 Hom.: 75

Bravo AF: 0.0687

Asia WGS AF: 0.133 AC: 463 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Nephrolithiasis, calcium oxalate (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		-0.27
PromoterAI		0.034	Neutral
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: rs2255183; hg19: chr20-7920604;