9-37429817-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:10O:1

Conservation

PhyloP100: -3.32

Publications

25 publications found

Variant links:

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

GRHPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHPR	NM_012203.2 link	c.579A>G	p.Ala193Ala	synonymous_variant	Exon 6 of 9	ENST00000318158.11	NP_036335.1	Q9UBQ7-1A0A384N605

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11 link	c.579A>G	p.Ala193Ala	synonymous_variant	Exon 6 of 9	1	NM_012203.2	ENSP00000313432.6		Q9UBQ7-1

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131215

AN:

152150

Hom.:

57029

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.910

AC XY:

656870

AN XY:

722142

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6136

12271

18407

24542

30678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21208

42416

63624

84832

106040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.862

AC:

131304

AN:

152268

Hom.:

57067

Cov.:

AF XY:

0.864

AC XY:

64311

AN XY:

74460

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

923

1846

2768

3691

4614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: Benign

Submissions summary: Uncertain:1Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type II

Uncertain:1Benign:3Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Nov 27, 2014

Clinical Biochemistry Laboratory, Health Services Laboratory

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:in vitro

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This is a RefSeq error. The reference base (c.579A) is the minor allele. This al lele (A) has been identified in 25.9% (2685/10378) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs309 458) and thus meets criteria to be classified as benign. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.0

(source)

DANN

Benign

0.63

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over