rs744731

Positions:

• chr4-17491220-T-C

Variant summary

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

The NM_000320.3(QDPR):​c.546-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,160 control chromosomes in the GnomAD database, including 4,349 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 0.22 (4349 hom., cov: 33)
• Consequence: QDPR NM_000320.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73

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 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QDPR	NM_000320.3	c.546-475A>G		intron_variant		ENST00000281243.10	NP_000311.2
QDPR	NM_001306140.2	c.453-475A>G		intron_variant			NP_001293069.1
QDPR	NR_156494.2	n.473-475A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10	c.546-475A>G		intron_variant		1	NM_000320.3	ENSP00000281243.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33719 AN: 152042 Hom.: 4346 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.222 AC: 33728 AN: 152160 Hom.: 4349 Cov.: 33 AF XY: 0.223 AC XY: 16604 AN XY: 74374

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.228

Alfa AF: 0.268 Hom.: 9715

Bravo AF: 0.209

Asia WGS AF: 0.233 AC: 812 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	0.0040
DANN	Benign	0.26

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: rs744731; hg19: chr4-17492843;