4-17501759-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000320.3(QDPR):c.396G>A(p.Leu132Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,613,742 control chromosomes in the GnomAD database, including 84,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6736 hom., cov: 32)

Exomes 𝑓: 0.32 ( 78249 hom. )

Consequence

QDPR
NM_000320.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.19

Publications

20 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 4-17501759-C-T is Benign according to our data. Variant chr4-17501759-C-T is described in ClinVar as Benign. ClinVar VariationId is 255819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
QDPR	NM_000320.3 link	c.396G>A	p.Leu132Leu	synonymous_variant	Exon 4 of 7	ENST00000281243.10	NP_000311.2
QDPR	NM_001306140.2 link	c.303G>A	p.Leu101Leu	synonymous_variant	Exon 3 of 6		NP_001293069.1
QDPR	NR_156494.2 link	n.432G>A		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10 link	c.396G>A	p.Leu132Leu	synonymous_variant	Exon 4 of 7	1	NM_000320.3	ENSP00000281243.5

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43314

AN:

151996

Hom.:

6730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.281

AC:

70687

AN:

251142

AF XY:

0.296

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.00903

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.320

AC:

468272

AN:

1461628

Hom.:

78249

Cov.:

AF XY:

0.324

AC XY:

235762

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.239

AC:

8012

AN:

33476

American (AMR)

AF:

0.160

AC:

7161

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

8443

AN:

26134

East Asian (EAS)

AF:

0.0190

AC:

754

AN:

39700

South Asian (SAS)

AF:

0.390

AC:

33624

AN:

86250

European-Finnish (FIN)

AF:

0.298

AC:

15879

AN:

53366

Middle Eastern (MID)

AF:

0.422

AC:

2428

AN:

5756

European-Non Finnish (NFE)

AF:

0.336

AC:

373091

AN:

1111840

Other (OTH)

AF:

0.313

AC:

18880

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18026

36052

54077

72103

90129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11830

23660

35490

47320

59150

<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:

0.285

AC:

43344

AN:

152114

Hom.:

6736

Cov.:

AF XY:

0.282

AC XY:

20998

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.234

AC:

9695

AN:

41500

American (AMR)

AF:

0.239

AC:

3647

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1086

AN:

3470

East Asian (EAS)

AF:

0.0187

AC:

AN:

5178

South Asian (SAS)

AF:

0.380

AC:

1831

AN:

4820

European-Finnish (FIN)

AF:

0.307

AC:

3249

AN:

10576

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.335

AC:

22763

AN:

67964

Other (OTH)

AF:

0.297

AC:

627

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1571

3141

4712

6282

7853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.316

Hom.:

12417

Bravo

AF:

0.271

Asia WGS

AF:

0.181

AC:

631

AN:

3478

EpiCase

AF:

0.344

EpiControl

AF:

0.342

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dihydropteridine reductase deficiency

Benign:5

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.2

(source)

DANN

Benign

0.73

PhyloP100

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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