rs2518608

Positions:

chr4-17511959-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000320.3(QDPR):c.96C>T(p.Ala32Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,610,798 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 151 hom. )

Consequence

QDPR
NM_000320.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.78

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:

QDPR (HGNC:):

QDPR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 4-17511959-G-A is Benign according to our data. Variant chr4-17511959-G-A is described in ClinVar as [Benign]. Clinvar id is 286391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-17511959-G-A is described in Lovd as [Benign]. Variant chr4-17511959-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00805 (1224/152060) while in subpopulation SAS AF= 0.0133 (64/4818). AF 95% confidence interval is 0.0124. There are 5 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QDPR	NM_000320.3 linkuse as main transcript	c.96C>T	p.Ala32Ala	synonymous_variant	1/7	ENST00000281243.10	NP_000311.2	P09417-1A0A140VKA9
QDPR	NM_001306140.2 linkuse as main transcript	c.96C>T	p.Ala32Ala	synonymous_variant	1/6		NP_001293069.1	P09417-2
QDPR	NR_156494.2 linkuse as main transcript	n.132C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10 linkuse as main transcript	c.96C>T	p.Ala32Ala	synonymous_variant	1/7	1	NM_000320.3	ENSP00000281243.5		P09417-1

Frequencies

GnomAD3 genomes

AF:

0.00808

AC:

1228

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00463

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00865

GnomAD3 exomes

AF:

0.0109

AC:

2582

AN:

236828

Hom.:

AF XY:

0.0119

AC XY:

1549

AN XY:

130558

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.00601

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.0122

AC:

17730

AN:

1458738

Hom.:

151

Cov.:

AF XY:

0.0125

AC XY:

9054

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.00658

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00805

AC:

1224

AN:

152060

Hom.:

Cov.:

AF XY:

0.00768

AC XY:

571

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.00463

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00856

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00737

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dihydropteridine reductase deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 29, 2016	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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