chr9-37436635-CCTCT-C

Variant names:

• chr9-37436635-CCTCT-C
• rs34302950
• NM_012203.2:c.866-12_866-9delTCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012203.2(GRHPR):​c.866-12_866-9delTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,516,864 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 28)
  • Exomes 𝑓: 0.00060 (5 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.455
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 9-37436635-CCTCT-C is Benign according to our data. Variant chr9-37436635-CCTCT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2731099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00354 (535/151140) while in subpopulation AFR AF = 0.0114 (470/41268). AF 95% confidence interval is 0.0105. There are 5 homozygotes in GnomAd4. There are 267 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.866-12_866-9delTCTC		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.866-12_866-9delTCTC		intron	N/A	ENSP00000313432.6	Q9UBQ7-1
	GRHPR	ENST00000460882.5	TSL:1	n.893-12_893-9delTCTC		intron	N/A
	GRHPR	ENST00000874646.1		c.974-12_974-9delTCTC		intron	N/A	ENSP00000544705.1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 536 AN: 151034 Hom.: 5 Cov.: 28

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000340

Gnomad OTH AF: 0.00338

GnomAD2 exomes AF: 0.00294 AC: 315 AN: 107182 AF XY: 0.00229

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.00585

Gnomad EAS exome AF: 0.000324

Gnomad FIN exome AF: 0.000176

Gnomad NFE exome AF: 0.000508

Gnomad OTH exome AF: 0.00107

GnomAD4 exome AF: 0.000601 AC: 821 AN: 1365724 Hom.: 5 AF XY: 0.000544 AC XY: 370 AN XY: 680136

African (AFR) AF: 0.0126 AC: 393 AN: 31246

American (AMR) AF: 0.00153 AC: 64 AN: 41810

Ashkenazi Jewish (ASJ) AF: 0.00395 AC: 97 AN: 24546

East Asian (EAS) AF: 0.000111 AC: 4 AN: 36126

South Asian (SAS) AF: 0.000198 AC: 16 AN: 80848

European-Finnish (FIN) AF: 0.000240 AC: 12 AN: 49898

Middle Eastern (MID) AF: 0.00201 AC: 11 AN: 5480

European-Non Finnish (NFE) AF: 0.000151 AC: 157 AN: 1039416

Other (OTH) AF: 0.00119 AC: 67 AN: 56354

GnomAD4 genome AF: 0.00354 AC: 535 AN: 151140 Hom.: 5 Cov.: 28 AF XY: 0.00362 AC XY: 267 AN XY: 73808

African (AFR) AF: 0.0114 AC: 470 AN: 41268

American (AMR) AF: 0.00125 AC: 19 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00347 AC: 12 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4786

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10316

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000340 AC: 23 AN: 67662

Other (OTH) AF: 0.00335 AC: 7 AN: 2090

Alfa AF: 0.00100 Hom.: 82

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

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: rs34302950; hg19: chr9-37436632;