9-37426527-C-T

Variant names:

• chr9-37426527-C-T
• rs2736664
• NM_012203.2:c.288-11C>T

Variant summary

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

The NM_012203.2(GRHPR):​c.288-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,547,970 control chromosomes in the GnomAD database, including 753,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66758 hom., cov: 32)
  • Exomes 𝑓: 0.99 (686878 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Scores: Splicing: ADA: 0.00001425
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:9
• Conservation: PhyloP100: 0.606
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-37426527-C-T is Benign according to our data. Variant chr9-37426527-C-T is described in ClinVar as Benign. ClinVar VariationId is 204220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 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.288-11C>T		intron	N/A	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.288-11C>T		intron	N/A	ENSP00000313432.6	Q9UBQ7-1
	GRHPR	ENST00000460882.5	TSL:1	n.315-11C>T		intron	N/A
	GRHPR	ENST00000493368.5	TSL:1	n.345-11C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141591 AN: 152092 Hom.: 66720 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.946

GnomAD2 exomes AF: 0.980 AC: 246419 AN: 251482 AF XY: 0.985

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.983

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.984

GnomAD4 exome AF: 0.991 AC: 1383775 AN: 1395760 Hom.: 686878 Cov.: 23 AF XY: 0.992 AC XY: 693138 AN XY: 698518

African (AFR) AF: 0.758 AC: 24372 AN: 32174

American (AMR) AF: 0.982 AC: 43832 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 25148 AN: 25744

East Asian (EAS) AF: 1.00 AC: 39344 AN: 39344

South Asian (SAS) AF: 0.999 AC: 84765 AN: 84866

European-Finnish (FIN) AF: 1.00 AC: 53369 AN: 53370

Middle Eastern (MID) AF: 0.964 AC: 5430 AN: 5632

European-Non Finnish (NFE) AF: 0.999 AC: 1050466 AN: 1051832

Other (OTH) AF: 0.981 AC: 57049 AN: 58146

GnomAD4 genome AF: 0.931 AC: 141683 AN: 152210 Hom.: 66758 Cov.: 32 AF XY: 0.934 AC XY: 69513 AN XY: 74446

African (AFR) AF: 0.766 AC: 31764 AN: 41460

American (AMR) AF: 0.968 AC: 14794 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3388 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.999 AC: 4820 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10620

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67932 AN: 68042

Other (OTH) AF: 0.946 AC: 2000 AN: 2114

Alfa AF: 0.940 Hom.: 23909

Bravo AF: 0.922

Asia WGS AF: 0.985 AC: 3426 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	1	2	Primary hyperoxaluria, type II (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.050
SpliceAI score (max)		0.0		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: rs2736664; hg19: chr9-37426524;