8-104330599-G-C

Variant summary

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

The ENST00000521601.1(DPYS):n.476-162C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,998 control chromosomes in the GnomAD database, including 28,543 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 0.59 (28543 hom., cov: 33)
• Consequence: DPYS ENST00000521601.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

Genes affected

DPYS (HGNC:3013): (dihydropyrimidinase) Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYS	ENST00000521601.1	n.476-162C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89466 AN: 151884 Hom.: 28482 Cov.: 33

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.589 AC: 89591 AN: 151998 Hom.: 28543 Cov.: 33 AF XY: 0.590 AC XY: 43874 AN XY: 74300

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.578

Alfa AF: 0.506 Hom.: 2444

Bravo AF: 0.611

Asia WGS AF: 0.750 AC: 2607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.69
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7010076; hg19: chr8-105342827;