rs200847843

Variant names:

• chr9-37422748-C-A
• rs200847843
• NM_012203.2:c.-3C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-37422748-C-A
• chr9-37422748-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012203.2(GRHPR):​c.-3C>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 0.000000701 in 1,426,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GRHPR NM_012203.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.-3C>A		5_prime_UTR	Exon 1 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.-3C>A		5_prime_UTR	Exon 1 of 9	ENSP00000313432.6	Q9UBQ7-1
	GRHPR	ENST00000460882.5	TSL:1	n.53C>A		non_coding_transcript_exon	Exon 1 of 9
	GRHPR	ENST00000493368.5	TSL:1	n.83C>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426222 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706850

African (AFR) AF: 0.00 AC: 0 AN: 32466

American (AMR) AF: 0.00 AC: 0 AN: 40840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 37266

South Asian (SAS) AF: 0.00 AC: 0 AN: 81658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4258

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095366

Other (OTH) AF: 0.00 AC: 0 AN: 58910

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		-1.0
PromoterAI		-0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs200847843; hg19: chr9-37422745;