rs2597775

Positions:

chr4-17501759-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000320.3(QDPR):c.396G>A(p.Leu132=) 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:7

Conservation

PhyloP100: 2.19

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-17501759-C-T is described in Lovd as [Benign].

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/exons	MANE
QDPR	NM_000320.3 linkuse as main transcript	c.396G>A	p.Leu132=	synonymous_variant	4/7	ENST00000281243.10
QDPR	NM_001306140.2 linkuse as main transcript	c.303G>A	p.Leu101=	synonymous_variant	3/6
QDPR	NR_156494.2 linkuse as main transcript	n.432G>A		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QDPR	ENST00000281243.10 linkuse as main transcript	c.396G>A	p.Leu132=	synonymous_variant	4/7	1	NM_000320.3	P1	P09417-1

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

GnomAD3 exomes

AF:

0.281

AC:

70687

AN:

251142

Hom.:

11506

AF XY:

0.296

AC XY:

40131

AN XY:

135734

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 SAS exome

AF:

0.391

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

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.0190

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.285

AC:

43344

AN:

152114

Hom.:

6736

Cov.:

AF XY:

0.282

AC XY:

20998

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.0187

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.321

Hom.:

10430

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dihydropteridine reductase deficiency

Benign:4

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.2

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over