rs309458

Variant names:

• chr9-37429817-A-G
• rs309458
• NM_012203.2:c.579A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-37429817-A-G
• chr9-37429817-A-C
• chr9-37429817-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012203.2(GRHPR):​c.579A>G​(p.Ala193Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 1,602,214 control chromosomes in the GnomAD database, including 656,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (57067 hom., cov: 35)
  • Exomes 𝑓: 0.91 (599321 hom.)
• Consequence: GRHPR NM_012203.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:10 O:1
• Conservation: PhyloP100: -3.32
• Publications: 25 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, Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-37429817-A-G is Benign according to our data. Variant chr9-37429817-A-G is described in ClinVar as Benign. ClinVar VariationId is 21490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	NM_012203.2	MANE Select	c.579A>G	p.Ala193Ala	synonymous	Exon 6 of 9	NP_036335.1	A0A384N605

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	ENST00000318158.11	TSL:1 MANE Select	c.579A>G	p.Ala193Ala	synonymous	Exon 6 of 9	ENSP00000313432.6	Q9UBQ7-1
	GRHPR	ENST00000460882.5	TSL:1	n.606A>G		non_coding_transcript_exon	Exon 6 of 9
	GRHPR	ENST00000874646.1		c.579A>G	p.Ala193Ala	synonymous	Exon 6 of 10	ENSP00000544705.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131215 AN: 152150 Hom.: 57029 Cov.: 35

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.883

GnomAD2 exomes AF: 0.894 AC: 224605 AN: 251230 AF XY: 0.900

Gnomad AFR exome AF: 0.742

Gnomad AMR exome AF: 0.864

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.924

Gnomad FIN exome AF: 0.882

Gnomad NFE exome AF: 0.914

Gnomad OTH exome AF: 0.903

GnomAD4 exome AF: 0.909 AC: 1317530 AN: 1449946 Hom.: 599321 Cov.: 30 AF XY: 0.910 AC XY: 656870 AN XY: 722142

African (AFR) AF: 0.745 AC: 24759 AN: 33248

American (AMR) AF: 0.866 AC: 38704 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 23529 AN: 26054

East Asian (EAS) AF: 0.907 AC: 35972 AN: 39646

South Asian (SAS) AF: 0.921 AC: 79231 AN: 86012

European-Finnish (FIN) AF: 0.882 AC: 47065 AN: 53348

Middle Eastern (MID) AF: 0.930 AC: 5352 AN: 5752

European-Non Finnish (NFE) AF: 0.916 AC: 1008569 AN: 1101146

Other (OTH) AF: 0.905 AC: 54349 AN: 60028

GnomAD4 genome AF: 0.862 AC: 131304 AN: 152268 Hom.: 57067 Cov.: 35 AF XY: 0.864 AC XY: 64311 AN XY: 74460

African (AFR) AF: 0.747 AC: 31025 AN: 41506

American (AMR) AF: 0.884 AC: 13527 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3156 AN: 3472

East Asian (EAS) AF: 0.921 AC: 4774 AN: 5186

South Asian (SAS) AF: 0.918 AC: 4435 AN: 4832

European-Finnish (FIN) AF: 0.877 AC: 9308 AN: 10612

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62149 AN: 68036

Other (OTH) AF: 0.882 AC: 1867 AN: 2116

Alfa AF: 0.895 Hom.: 145781

Bravo AF: 0.857

Asia WGS AF: 0.900 AC: 3130 AN: 3478

EpiCase AF: 0.922

EpiControl AF: 0.921

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	1	3	Primary hyperoxaluria, type II (5)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.0
DANN	Benign	0.63
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs309458; hg19: chr9-37429814; COSMIC: COSV58944398; COSMIC: COSV58944398;