Genetic Variant QDPR:c.546-475A>G (chr4-17491220-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000320.3(QDPR):c.546-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,160 control chromosomes in the GnomAD database, including 4,349 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4349 hom., cov: 33)

Consequence

QDPR
NM_000320.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.73

Publications

4 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

QDPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000320.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
QDPR	NM_000320.3	MANE Select	c.546-475A>G	intron	N/A	NP_000311.2	A0A140VKA9
QDPR	NM_001306140.2		c.453-475A>G	intron	N/A	NP_001293069.1	P09417-2
QDPR	NR_156494.2		n.473-475A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
QDPR	ENST00000281243.10	TSL:1 MANE Select	c.546-475A>G	intron	N/A	ENSP00000281243.5	P09417-1
QDPR	ENST00000910937.1		c.621-475A>G	intron	N/A	ENSP00000580996.1
QDPR	ENST00000910936.1		c.594-475A>G	intron	N/A	ENSP00000580995.1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33719

AN:

152042

Hom.:

4346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.222

AC:

33728

AN:

152160

Hom.:

4349

Cov.:

AF XY:

0.223

AC XY:

16604

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.102

AC:

4222

AN:

41534

American (AMR)

AF:

0.196

AC:

2999

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3472

East Asian (EAS)

AF:

0.246

AC:

1275

AN:

5180

South Asian (SAS)

AF:

0.171

AC:

826

AN:

4828

European-Finnish (FIN)

AF:

0.315

AC:

3321

AN:

10550

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19463

AN:

67988

Other (OTH)

AF:

0.228

AC:

481

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1333

2666

3998

5331

6664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.265

Hom.:

21736

Bravo

AF:

0.209

Asia WGS

AF:

0.233

AC:

812

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0040

(source)

DANN

Benign

0.26

PhyloP100

-3.7

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over