rs4698599

Variant names:

• chr4-17476645-G-A
• rs4698599
• ENST00000513615.5:c.*119+10534C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.99).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000513615.5	c.*119+10534C>T		intron_variant	Intron 6 of 6	2		ENSP00000422759.1

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

African (AFR) AF: 0.437 AC: 18071 AN: 41374

American (AMR) AF: 0.390 AC: 5958 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1379 AN: 5164

South Asian (SAS) AF: 0.323 AC: 1555 AN: 4814

European-Finnish (FIN) AF: 0.427 AC: 4502 AN: 10540

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30920 AN: 67960

Other (OTH) AF: 0.404 AC: 853 AN: 2110

Alfa AF: 0.443 Hom.: 25967

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
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4698599; hg19: chr4-17478268;