4-17488717-T-G

Variant names:

• chr4-17488717-T-G
• rs2252995
• NM_000320.3:c.630-1481A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000320.3(QDPR):​c.630-1481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,162 control chromosomes in the GnomAD database, including 32,688 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 0.65 (32688 hom., cov: 33)
• Consequence: QDPR NM_000320.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 2 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QDPR	NM_000320.3	c.630-1481A>C		intron_variant	Intron 6 of 6	ENST00000281243.10	NP_000311.2
QDPR	NM_001306140.2	c.537-1481A>C		intron_variant	Intron 5 of 5		NP_001293069.1
QDPR	NR_156494.2	n.557-1481A>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10	c.630-1481A>C		intron_variant	Intron 6 of 6	1	NM_000320.3	ENSP00000281243.5

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99080 AN: 152044 Hom.: 32660 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.652 AC: 99155 AN: 152162 Hom.: 32688 Cov.: 33 AF XY: 0.660 AC XY: 49076 AN XY: 74396

African (AFR) AF: 0.567 AC: 23523 AN: 41488

American (AMR) AF: 0.601 AC: 9187 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1944 AN: 3472

East Asian (EAS) AF: 0.766 AC: 3961 AN: 5168

South Asian (SAS) AF: 0.682 AC: 3289 AN: 4824

European-Finnish (FIN) AF: 0.795 AC: 8423 AN: 10598

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46643 AN: 68010

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.669 Hom.: 4408

Bravo AF: 0.629

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
DANN	Benign	0.40
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2252995; hg19: chr4-17490340;