4-17507131-C-T

Variant names:

• chr4-17507131-C-T
• rs2597778
• NM_000320.3:c.198+2140G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
QDPR	NM_000320.3	c.198+2140G>A		intron_variant	Intron 2 of 6	ENST00000281243.10	NP_000311.2
QDPR	NM_001306140.2	c.106-2656G>A		intron_variant	Intron 1 of 5		NP_001293069.1
QDPR	NR_156494.2	n.234+2140G>A		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QDPR	ENST00000281243.10	c.198+2140G>A		intron_variant	Intron 2 of 6	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

African (AFR) AF: 0.557 AC: 23089 AN: 41448

American (AMR) AF: 0.602 AC: 9197 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2005 AN: 3468

East Asian (EAS) AF: 0.770 AC: 3981 AN: 5170

South Asian (SAS) AF: 0.689 AC: 3330 AN: 4830

European-Finnish (FIN) AF: 0.796 AC: 8413 AN: 10568

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46856 AN: 67948

Other (OTH) AF: 0.658 AC: 1388 AN: 2110

Alfa AF: 0.671 Hom.: 11711

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2597778; hg19: chr4-17508754;