4-17511933-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
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
NM_000320.3 intron
Scores
2
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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 GnomAd4 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: 1033AN: 152084Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00673 AC: 1557AN: 231192Hom.: 10 AF XY: 0.00662 AC XY: 846AN XY: 127862
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GnomAD4 exome AF: 0.00728 AC: 10603AN: 1455534Hom.: 47 Cov.: 32 AF XY: 0.00728 AC XY: 5272AN XY: 724112
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GnomAD4 genome AF: 0.00678 AC: 1032AN: 152202Hom.: 3 Cov.: 31 AF XY: 0.00662 AC XY: 493AN XY: 74436
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 15, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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
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BayesDel_noAF
Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at