rs149373480

chr4-17511933-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000320.3(QDPR):c.105+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,607,736 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0073 (47 hom.)
• Consequence: QDPR NM_000320.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0500

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 4-17511933-C-T is Benign according to our data. Variant chr4-17511933-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-17511933-C-T is described in Lovd as [Likely_benign]. Variant chr4-17511933-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00678 (1032/152202) while in subpopulation NFE AF= 0.00908 (617/67976). AF 95% confidence interval is 0.00848. There are 3 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QDPR	NM_000320.3	c.105+17G>A		intron_variant		ENST00000281243.10
QDPR	NM_001306140.2	c.105+17G>A		intron_variant
QDPR	NR_156494.2	n.141+17G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QDPR	ENST00000281243.10	c.105+17G>A		intron_variant		1	NM_000320.3	P1

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 1033 AN: 152084 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00908

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00673 AC: 1557 AN: 231192 Hom.: 10 AF XY: 0.00662 AC XY: 846 AN XY: 127862

Gnomad AFR exome AF: 0.00410

Gnomad AMR exome AF: 0.00636

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.00498

Gnomad NFE exome AF: 0.00907

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.00728 AC: 10603 AN: 1455534 Hom.: 47 Cov.: 32 AF XY: 0.00728 AC XY: 5272 AN XY: 724112

Gnomad4 AFR exome AF: 0.00348

Gnomad4 AMR exome AF: 0.00685

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00252

Gnomad4 FIN exome AF: 0.00553

Gnomad4 NFE exome AF: 0.00780

Gnomad4 OTH exome AF: 0.00826

GnomAD4 genome AF: 0.00678 AC: 1032 AN: 152202 Hom.: 3 Cov.: 31 AF XY: 0.00662 AC XY: 493 AN XY: 74436

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00604

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00915 Hom.: 0

Bravo AF: 0.00722

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 15, 2017	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

-

- -

Dihydropteridine reductase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	5.8
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149373480; hg19: chr4-17513556;