chr4-17511933-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0500

Publications

0 publications found

Variant links:

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]

QDPR Gene-Disease associations (from GenCC):

dihydropteridine reductase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

QDPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 445851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
QDPR	NM_000320.3 link	c.105+17G>A	intron_variant	Intron 1 of 6	ENST00000281243.10	NP_000311.2	P09417-1A0A140VKA9
QDPR	NM_001306140.2 link	c.105+17G>A	intron_variant	Intron 1 of 5		NP_001293069.1	P09417-2
QDPR	NR_156494.2 link	n.141+17G>A	intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10 link	c.105+17G>A		intron_variant	Intron 1 of 6	1	NM_000320.3	ENSP00000281243.5		P09417-1

Frequencies

GnomAD3 genomes

AF:

0.00679

AC:

1033

AN:

152084

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00673

AC:

1557

AN:

231192

AF XY:

0.00662

show subpopulations

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 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.:

Cov.:

AF XY:

0.00728

AC XY:

5272

AN XY:

724112

show subpopulations

African (AFR)

AF:

0.00348

AC:

116

AN:

33304

American (AMR)

AF:

0.00685

AC:

304

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

409

AN:

26006

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39488

South Asian (SAS)

AF:

0.00252

AC:

217

AN:

85954

European-Finnish (FIN)

AF:

0.00553

AC:

282

AN:

50984

Middle Eastern (MID)

AF:

0.0209

AC:

120

AN:

5744

European-Non Finnish (NFE)

AF:

0.00780

AC:

8658

AN:

1109610

Other (OTH)

AF:

0.00826

AC:

496

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

535

1071

1606

2142

2677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00678

AC:

1032

AN:

152202

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

493

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41558

American (AMR)

AF:

0.00771

AC:

118

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00604

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00908

AC:

617

AN:

67976

Other (OTH)

AF:

0.0114

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00915

Hom.:

Bravo

AF:

0.00722

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dihydropteridine reductase deficiency

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.8

(source)

DANN

Benign

0.96

PhyloP100

0.050

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over