4-17507131-C-T

Position:

• chr4-17507131-C-T

Variant summary

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

The NM_000320.3(QDPR):​c.198+2140G>A 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 152,022 control chromosomes in the GnomAD database, including 32,697 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 (32697 hom., cov: 32)
• Consequence: QDPR NM_000320.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QDPR	NM_000320.3	c.198+2140G>A		intron_variant		ENST00000281243.10	NP_000311.2
QDPR	NM_001306140.2	c.106-2656G>A		intron_variant			NP_001293069.1
QDPR	NR_156494.2	n.234+2140G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10	c.198+2140G>A		intron_variant		1	NM_000320.3	ENSP00000281243.5

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99023 AN: 151904 Hom.: 32690 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.652 AC: 99068 AN: 152022 Hom.: 32697 Cov.: 32 AF XY: 0.659 AC XY: 48954 AN XY: 74328

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.658

Alfa AF: 0.676 Hom.: 6878

Bravo AF: 0.630

Asia WGS AF: 0.699 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.079
DANN	Benign	0.46

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: rs2597778; hg19: chr4-17508754;