NM_012203.2:c.288-11C>T

Variant names:

• chr9-37426527-C-T
• rs2736664
• NM_012203.2:c.288-11C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012203.2(GRHPR):​c.288-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,547,970 control chromosomes in the GnomAD database, including 753,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66758 hom., cov: 32)
  • Exomes 𝑓: 0.99 (686878 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Scores: Splicing: ADA: 0.00001425
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:9
• Conservation: PhyloP100: 0.606

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-37426527-C-T is Benign according to our data. Variant chr9-37426527-C-T is described in ClinVar as [Benign]. Clinvar id is 204220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-37426527-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHPR	NM_012203.2	c.288-11C>T		intron_variant	Intron 3 of 8	ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11	c.288-11C>T		intron_variant	Intron 3 of 8	1	NM_012203.2	ENSP00000313432.6

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141591 AN: 152092 Hom.: 66720 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.946

GnomAD3 exomes AF: 0.980 AC: 246419 AN: 251482 Hom.: 121159 AF XY: 0.985 AC XY: 133813 AN XY: 135918

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.983

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.999

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.984

GnomAD4 exome AF: 0.991 AC: 1383775 AN: 1395760 Hom.: 686878 Cov.: 23 AF XY: 0.992 AC XY: 693138 AN XY: 698518

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.981

GnomAD4 genome AF: 0.931 AC: 141683 AN: 152210 Hom.: 66758 Cov.: 32 AF XY: 0.934 AC XY: 69513 AN XY: 74446

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.968

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.946

Alfa AF: 0.958 Hom.: 13594

Bravo AF: 0.922

Asia WGS AF: 0.985 AC: 3426 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 27, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This is a RefSeq error. The reference base (c.288-11C) is the minor allele. This allele (C) has been identified in 23.8% (2472/10406) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 2736664) and thus meets criteria to be classified as benign. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary hyperoxaluria, type II Uncertain:1 Benign:2

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.050
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: rs2736664; hg19: chr9-37426524;