chr9-37428581-C-T

Position:

• chr9-37428581-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000318158.11(GRHPR):​c.493+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,579,830 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (8 hom., cov: 33)
  • Exomes 𝑓: 0.012 (127 hom.)
• Consequence: GRHPR ENST00000318158.11 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0500

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=-0.8).
• BP6: Variant 9-37428581-C-T is Benign according to our data. Variant chr9-37428581-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00855 (1302/152192) while in subpopulation NFE AF= 0.0131 (892/68000). AF 95% confidence interval is 0.0124. There are 8 homozygotes in gnomad4. There are 603 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHPR	NM_012203.2	c.493+9C>T		intron_variant		ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11	c.493+9C>T		intron_variant		1	NM_012203.2	ENSP00000313432	P1

Frequencies

GnomAD3 genomes AF: 0.00857 AC: 1304 AN: 152074 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00904 AC: 2219 AN: 245430 Hom.: 20 AF XY: 0.00950 AC XY: 1265 AN XY: 133184

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00713

Gnomad FIN exome AF: 0.0154

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.00969

GnomAD4 exome AF: 0.0116 AC: 16502 AN: 1427638 Hom.: 127 Cov.: 27 AF XY: 0.0115 AC XY: 8155 AN XY: 712030

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.00369

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00726

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.00953

GnomAD4 genome AF: 0.00855 AC: 1302 AN: 152192 Hom.: 8 Cov.: 33 AF XY: 0.00810 AC XY: 603 AN XY: 74422

Gnomad4 AFR AF: 0.00205

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00645 Hom.: 4

Bravo AF: 0.00756

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary hyperoxaluria, type II Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs41303225; hg19: chr9-37428578; COSMIC: COSV105894202; COSMIC: COSV105894202;