9-37436635-CCTCTCTCTCTCT-CCTCTCTCTCTCTCT

Variant names:

• chr9-37436635-C-CCT
• rs34302950
• NM_012203.2:c.866-10_866-9dupTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_012203.2(GRHPR):​c.866-10_866-9dupTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,516,950 control chromosomes in the GnomAD database, including 7,536 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1896 hom., cov: 28)
  • Exomes 𝑓: 0.18 (5640 hom.)
• Consequence: GRHPR NM_012203.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: -0.689
• 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 -16 ACMG points.

• BP6: Variant 9-37436635-C-CCT is Benign according to our data. Variant chr9-37436635-C-CCT is described in ClinVar as Benign. ClinVar VariationId is 204227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHPR	NM_012203.2	c.866-10_866-9dupTC		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11	c.866-26_866-25insCT		intron_variant	Intron 8 of 8	1	NM_012203.2	ENSP00000313432.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22868 AN: 150990 Hom.: 1895 Cov.: 28

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.329 AC: 35296 AN: 107182 AF XY: 0.344

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.392

Gnomad EAS exome AF: 0.0272

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.175 AC: 239486 AN: 1365854 Hom.: 5640 Cov.: 29 AF XY: 0.175 AC XY: 118973 AN XY: 680316

African (AFR) AF: 0.0930 AC: 2905 AN: 31252

American (AMR) AF: 0.0847 AC: 3551 AN: 41930

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 5985 AN: 24576

East Asian (EAS) AF: 0.00396 AC: 144 AN: 36392

South Asian (SAS) AF: 0.125 AC: 10151 AN: 80906

European-Finnish (FIN) AF: 0.174 AC: 8712 AN: 50066

Middle Eastern (MID) AF: 0.219 AC: 1204 AN: 5498

European-Non Finnish (NFE) AF: 0.190 AC: 197206 AN: 1038810

Other (OTH) AF: 0.171 AC: 9628 AN: 56424

GnomAD4 genome AF: 0.151 AC: 22884 AN: 151096 Hom.: 1896 Cov.: 28 AF XY: 0.149 AC XY: 10996 AN XY: 73784

African (AFR) AF: 0.0963 AC: 3975 AN: 41256

American (AMR) AF: 0.128 AC: 1937 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 902 AN: 3458

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5168

South Asian (SAS) AF: 0.118 AC: 563 AN: 4784

European-Finnish (FIN) AF: 0.181 AC: 1869 AN: 10298

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 12971 AN: 67652

Other (OTH) AF: 0.172 AC: 359 AN: 2090

Alfa AF: 0.107 Hom.: 82

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type II Uncertain:1 Benign:1

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

May 05, 2011

GeneReviews

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

- -

not provided Benign:2

Jun 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV106059174; COSMIC: COSV106059174;