rs10973332

Variant names:

• chr9-37422678-C-A
• rs10973332
• ENST00000493368.5:n.13C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-37422678-C-A
• chr9-37422678-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000874644.1(GRHPR):​c.-73C>A variant causes a 5 prime UTR 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 ENST00000874644.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61
• Publications: 4 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: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000294170 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1226850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000874644.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	NM_012203.2	MANE Select	c.-73C>A		upstream_gene	N/A	NP_036335.1	A0A384N605

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	ENST00000493368.5	TSL:1	n.13C>A		non_coding_transcript_exon	Exon 1 of 5
	GRHPR	ENST00000874644.1		c.-73C>A		5_prime_UTR	Exon 1 of 5	ENSP00000544703.1
	GRHPR	ENST00000926738.1		c.-73C>A		5_prime_UTR	Exon 1 of 3	ENSP00000596797.1

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

African (AFR) AF: 0.0806 AC: 2065 AN: 25626

American (AMR) AF: 0.0299 AC: 1062 AN: 35490

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 1085 AN: 23228

East Asian (EAS) AF: 0.379 AC: 13001 AN: 34300

South Asian (SAS) AF: 0.156 AC: 11407 AN: 72946

European-Finnish (FIN) AF: 0.0425 AC: 2024 AN: 47614

Middle Eastern (MID) AF: 0.0482 AC: 167 AN: 3462

European-Non Finnish (NFE) AF: 0.0436 AC: 34582 AN: 793878

Other (OTH) AF: 0.0746 AC: 3530 AN: 47346

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

African (AFR) AF: 0.0792 AC: 3290 AN: 41554

American (AMR) AF: 0.0465 AC: 711 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2211 AN: 5152

South Asian (SAS) AF: 0.163 AC: 785 AN: 4828

European-Finnish (FIN) AF: 0.0373 AC: 396 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2965 AN: 68012

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0227 Hom.: 16

Bravo AF: 0.0711

Asia WGS AF: 0.242 AC: 839 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.46
PhyloP100		-1.6
PromoterAI		0.054	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10973332; hg19: chr9-37422675; COSMIC: COSV58943437; COSMIC: COSV58943437;