dbSNP rs149373480: QDPR:c.105+17G>A (chr4-17511933-C-T) – ACMG Classification: Benign (-20 pts)

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: 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 -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

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.105+17G>A	intron	N/A	NP_000311.2	A0A140VKA9
QDPR	NM_001306140.2		c.105+17G>A	intron	N/A	NP_001293069.1	P09417-2
QDPR	NR_156494.2		n.141+17G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
QDPR	ENST00000281243.10	TSL:1 MANE Select	c.105+17G>A	intron	N/A	ENSP00000281243.5	P09417-1
QDPR	ENST00000910937.1		c.105+17G>A	intron	N/A	ENSP00000580996.1
QDPR	ENST00000910936.1		c.105+17G>A	intron	N/A	ENSP00000580995.1

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Dihydropteridine reductase deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over