NM_012203.2:c.83+52delG

Variant names:

• chr9-37422883-CG-C
• rs35891798
• NM_012203.2:c.83+52delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012203.2(GRHPR):​c.83+52delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,363,358 control chromosomes in the GnomAD database, including 21,753 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1901 hom., cov: 29)
  • Exomes 𝑓: 0.18 (19852 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -0.433
• Publications: 2 publications found

Genes affected

GRHPR (HGNC:4570): (glyoxylate and hydroxypyruvate reductase) This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in metabolism. Type II hyperoxaluria is caused by mutations in this gene. [provided by RefSeq, Jul 2008]

GRHPR Gene-Disease associations (from GenCC):

• primary hyperoxaluria type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet

ENSG00000294170 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-37422883-CG-C is Benign according to our data. Variant chr9-37422883-CG-C is described in ClinVar as Benign. ClinVar VariationId is 204218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHPR	NM_012203.2	c.83+52delG		intron_variant	Intron 1 of 8	ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11	c.83+51delG		intron_variant	Intron 1 of 8	1	NM_012203.2	ENSP00000313432.6

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22613 AN: 152074 Hom.: 1899 Cov.: 29

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.166 AC: 24285 AN: 146674 AF XY: 0.165

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.0394

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.176 AC: 213228 AN: 1211166 Hom.: 19852 Cov.: 12 AF XY: 0.175 AC XY: 105998 AN XY: 604794

African (AFR) AF: 0.0719 AC: 1993 AN: 27706

American (AMR) AF: 0.188 AC: 6586 AN: 35042

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 5812 AN: 23588

East Asian (EAS) AF: 0.0304 AC: 1059 AN: 34860

South Asian (SAS) AF: 0.131 AC: 9862 AN: 75470

European-Finnish (FIN) AF: 0.159 AC: 7472 AN: 46928

Middle Eastern (MID) AF: 0.242 AC: 897 AN: 3704

European-Non Finnish (NFE) AF: 0.187 AC: 170613 AN: 912376

Other (OTH) AF: 0.174 AC: 8934 AN: 51492

GnomAD4 genome AF: 0.149 AC: 22617 AN: 152192 Hom.: 1901 Cov.: 29 AF XY: 0.148 AC XY: 10991 AN XY: 74396

African (AFR) AF: 0.0753 AC: 3128 AN: 41540

American (AMR) AF: 0.183 AC: 2793 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.0428 AC: 221 AN: 5168

South Asian (SAS) AF: 0.129 AC: 623 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1669 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12646 AN: 67990

Other (OTH) AF: 0.170 AC: 360 AN: 2116

Alfa AF: 0.176 Hom.: 460

Bravo AF: 0.149

Asia WGS AF: 0.0960 AC: 337 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary hyperoxaluria, type II Uncertain:1 Benign:1

Jan 23, 2024

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43
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: rs35891798; hg19: chr9-37422880; COSMIC: COSV58942441; COSMIC: COSV58942441;