9-37422678-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000493368.5(GRHPR):n.13C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,236,150 control chromosomes in the GnomAD database, including 5,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (779 hom., cov: 32)
  • Exomes 𝑓: 0.064 (4692 hom.)
• Consequence: GRHPR ENST00000493368.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-37422678-C-A is Benign according to our data. Variant chr9-37422678-C-A is described in ClinVar as [Benign]. Clinvar id is 1226850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHPR	NM_012203.2			upstream_gene_variant		ENST00000318158.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHPR	ENST00000318158.11			upstream_gene_variant		1	NM_012203.2	P1

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10701 AN: 152142 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.0636 AC: 68923 AN: 1083890 Hom.: 4692 Cov.: 15 AF XY: 0.0669 AC XY: 36618 AN XY: 547352

Gnomad4 AFR exome AF: 0.0806

Gnomad4 AMR exome AF: 0.0299

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0425

Gnomad4 NFE exome AF: 0.0436

Gnomad4 OTH exome AF: 0.0746

GnomAD4 genome AF: 0.0703 AC: 10708 AN: 152260 Hom.: 779 Cov.: 32 AF XY: 0.0734 AC XY: 5462 AN XY: 74462

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0227 Hom.: 16

Bravo AF: 0.0711

Asia WGS AF: 0.242 AC: 839 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.0
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10973332; hg19: chr9-37422675; COSMIC: COSV58943437; COSMIC: COSV58943437;