9-37436635-CCTCTCTCTCTCT-CCTCTCTCTCT

Variant names:

• chr9-37436635-CCT-C
• rs34302950
• NM_012203.2:c.866-10_866-9delTC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_012203.2(GRHPR):​c.866-10_866-9delTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,204,624 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0099 (0 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00987 (10403/1053652) while in subpopulation EAS AF= 0.0318 (618/19424). AF 95% confidence interval is 0.0297. There are 0 homozygotes in gnomad4_exome. There are 4957 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHPR	NM_012203.2	c.866-10_866-9delTC		intron_variant	Intron 8 of 8	ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11	c.866-25_866-24delCT		intron_variant	Intron 8 of 8	1	NM_012203.2	ENSP00000313432.6

Frequencies

GnomAD3 genomes AF: 0.000265 AC: 40 AN: 150870 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000396

Gnomad ASJ AF: 0.00376

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.00987 AC: 10403 AN: 1053652 Hom.: 0 AF XY: 0.00961 AC XY: 4957 AN XY: 516064

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.0318

Gnomad4 SAS exome AF: 0.00705

Gnomad4 FIN exome AF: 0.0159

Gnomad4 NFE exome AF: 0.00889

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.000265 AC: 40 AN: 150972 Hom.: 0 Cov.: 28 AF XY: 0.000339 AC XY: 25 AN XY: 73710

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000395

Gnomad4 ASJ AF: 0.00376

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000627

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.000479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34302950; hg19: chr9-37436632;