rs4698599

Positions:

• chr4-17476645-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513615.5(QDPR):​c.*119+10534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,898 control chromosomes in the GnomAD database, including 14,192 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 0.43 (14192 hom., cov: 31)
• Consequence: QDPR ENST00000513615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000513615.5	c.*119+10534C>T		intron_variant		2		ENSP00000422759

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65291 AN: 151780 Hom.: 14176 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.430 AC: 65343 AN: 151898 Hom.: 14192 Cov.: 31 AF XY: 0.426 AC XY: 31578 AN XY: 74208

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.404

Alfa AF: 0.442 Hom.: 20505

Bravo AF: 0.434

Asia WGS AF: 0.306 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4698599; hg19: chr4-17478268;