Genetic Variant ENST00000493368.5:n.13C>A (chr9-37422678-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.61

Publications

4 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Myriad Women's Health

GRHPR links:

ENSG00000294170 (HGNC:):

ENSG00000294170 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000493368.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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: ENST00000493368.5. 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
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.:

show subpopulations

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.:

AF XY:

0.0669

AC XY:

36618

AN XY:

547352

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

3150

6299

9449

12598

15748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1294

2588

3882

5176

6470

<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:

0.0703

AC:

10708

AN:

152260

Hom.:

779

Cov.:

AF XY:

0.0734

AC XY:

5462

AN XY:

74462

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0436

AC:

2965

AN:

68012

Other (OTH)

AF:

0.0723

AC:

153

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

455

910

1364

1819

2274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0227

Hom.:

Bravo

AF:

0.0711

Asia WGS

AF:

0.242

AC:

839

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.0

(source)

DANN

Benign

0.46

PhyloP100

-1.6

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over