4-17488717-T-G

Position:

• chr4-17488717-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
QDPR	NM_000320.3	c.630-1481A>C		intron_variant		ENST00000281243.10
QDPR	NM_001306140.2	c.537-1481A>C		intron_variant
QDPR	NR_156494.2	n.557-1481A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QDPR	ENST00000281243.10	c.630-1481A>C		intron_variant		1	NM_000320.3	P1

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

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.650

Alfa AF: 0.673 Hom.: 4283

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

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

Other links and lift over

dbSNP: rs2252995; hg19: chr4-17490340;