4-17486884-GC-G

Position:

• chr4-17486884-GC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000320.3(QDPR):​c.*246del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 535,556 control chromosomes in the GnomAD database, including 21,708 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5054 hom., cov: 25)
  • Exomes 𝑓: 0.28 (16654 hom.)
• Consequence: QDPR NM_000320.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.148

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 -16 ACMG points.

• BP6: Variant 4-17486884-GC-G is Benign according to our data. Variant chr4-17486884-GC-G is described in ClinVar as [Benign]. Clinvar id is 348148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QDPR	NM_000320.3	c.*246del		3_prime_UTR_variant	7/7	ENST00000281243.10
QDPR	NM_001306140.2	c.*246del		3_prime_UTR_variant	6/6
QDPR	NR_156494.2	n.908del		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QDPR	ENST00000281243.10	c.*246del		3_prime_UTR_variant	7/7	1	NM_000320.3	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36462 AN: 152046 Hom.: 5052 Cov.: 25

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.279 AC: 107069 AN: 383394 Hom.: 16654 Cov.: 0 AF XY: 0.287 AC XY: 58470 AN XY: 203682

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.0191

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.240 AC: 36465 AN: 152162 Hom.: 5054 Cov.: 25 AF XY: 0.238 AC XY: 17687 AN XY: 74370

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.247

Alfa AF: 0.274 Hom.: 749

Bravo AF: 0.223

Asia WGS AF: 0.169 AC: 590 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BH4-Deficient Hyperphenylalaninemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs71810044; hg19: chr4-17488507;