rs2514675

Positions:

• chr8-104372703-G-A
• chr8-104372703-G-C

Variant summary

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

The ENST00000521601.1(DPYS):​n.328+8481C>T 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 0.462 in 152,104 control chromosomes in the GnomAD database, including 19,980 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 0.46 (19980 hom., cov: 33)
• Consequence: DPYS ENST00000521601.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYS	ENST00000521601.1	n.328+8481C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70222 AN: 151986 Hom.: 19973 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.462 AC: 70237 AN: 152104 Hom.: 19980 Cov.: 33 AF XY: 0.458 AC XY: 34027 AN XY: 74332

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.488

Alfa AF: 0.546 Hom.: 3074

Bravo AF: 0.443

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2514675; hg19: chr8-105384931;