NM_012203.2:c.866-14_866-9delTCTCTC

Variant names:

• chr9-37436635-CCTCTCT-C
• rs34302950
• NM_012203.2:c.866-14_866-9delTCTCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012203.2(GRHPR):​c.866-14_866-9delTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,525,216 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 28)
  • Exomes 𝑓: 0.00073 (3 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.455
• Publications: 0 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

ACMG classification

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

• BP6: Variant 9-37436635-CCTCTCT-C is Benign according to our data. Variant chr9-37436635-CCTCTCT-C is described in ClinVar as Benign. ClinVar VariationId is 1572176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00531 (803/151142) while in subpopulation AFR AF = 0.0177 (731/41266). AF 95% confidence interval is 0.0166. There are 4 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012203.2. 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
	GRHPR	NM_012203.2	MANE Select	c.866-14_866-9delTCTCTC		intron	N/A	NP_036335.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	ENST00000318158.11	TSL:1 MANE Select	c.866-25_866-20delCTCTCT		intron	N/A	ENSP00000313432.6
	GRHPR	ENST00000460882.5	TSL:1	n.893-25_893-20delCTCTCT		intron	N/A
	GRHPR	ENST00000480596.5	TSL:2	n.1567-25_1567-20delCTCTCT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 798 AN: 151036 Hom.: 4 Cov.: 28

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.00242

GnomAD2 exomes AF: 0.00432 AC: 463 AN: 107182 AF XY: 0.00330

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.00529

Gnomad ASJ exome AF: 0.00361

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000581

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.000728 AC: 1000 AN: 1374074 Hom.: 3 AF XY: 0.000649 AC XY: 444 AN XY: 684078

African (AFR) AF: 0.0183 AC: 576 AN: 31454

American (AMR) AF: 0.00186 AC: 78 AN: 41988

Ashkenazi Jewish (ASJ) AF: 0.00235 AC: 58 AN: 24670

East Asian (EAS) AF: 0.00 AC: 0 AN: 36554

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81086

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50258

Middle Eastern (MID) AF: 0.00272 AC: 15 AN: 5512

European-Non Finnish (NFE) AF: 0.000172 AC: 180 AN: 1045828

Other (OTH) AF: 0.00160 AC: 91 AN: 56724

GnomAD4 genome AF: 0.00531 AC: 803 AN: 151142 Hom.: 4 Cov.: 28 AF XY: 0.00518 AC XY: 382 AN XY: 73810

African (AFR) AF: 0.0177 AC: 731 AN: 41266

American (AMR) AF: 0.00276 AC: 42 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3458

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10316

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000251 AC: 17 AN: 67666

Other (OTH) AF: 0.00239 AC: 5 AN: 2090

Alfa AF: 0.000459 Hom.: 82

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34302950; hg19: chr9-37436632;