rs2597758

Positions:

• chr4-17483858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513615.5(QDPR):​c.*119+3321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,934 control chromosomes in the GnomAD database, including 28,998 homozygotes. 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: 𝑓 0.61 (28998 hom., cov: 31)
• Consequence: QDPR ENST00000513615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

QDPR (HGNC:9752): (quinoid dihydropteridine reductase) This gene encodes the enzyme dihydropteridine reductase, which catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin. This enzyme is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems. Mutations in this gene resulting in QDPR deficiency include aberrant splicing, amino acid substitutions, insertions, or premature terminations. Dihydropteridine reductase deficiency presents as atypical phenylketonuria due to insufficient production of biopterin, a cofactor for phenylalanine hydroxylase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QDPR	ENST00000513615.5	c.*119+3321G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92706 AN: 151816 Hom.: 28981 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.611 AC: 92765 AN: 151934 Hom.: 28998 Cov.: 31 AF XY: 0.618 AC XY: 45929 AN XY: 74266

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.624

Alfa AF: 0.647 Hom.: 14200

Bravo AF: 0.588

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.59
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2597758; hg19: chr4-17485481;