rs2514675

Variant names:

• chr8-104372703-G-A
• rs2514675
• ENST00000908793.1:c.*14+8481C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000908793.1(DPYS):​c.*14+8481C>T variant causes a intron 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 ENST00000908793.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 3 publications found

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]

DPYS Gene-Disease associations (from GenCC):

• dihydropyrimidinuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908793.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYS	ENST00000908793.1		c.*14+8481C>T		intron	N/A	ENSP00000578852.1
	DPYS	ENST00000908791.1		c.*14+8481C>T		intron	N/A	ENSP00000578850.1
	DPYS	ENST00000908792.1		c.*14+8481C>T		intron	N/A	ENSP00000578851.1

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

African (AFR) AF: 0.135 AC: 5597 AN: 41518

American (AMR) AF: 0.493 AC: 7544 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1328 AN: 5186

South Asian (SAS) AF: 0.470 AC: 2261 AN: 4814

European-Finnish (FIN) AF: 0.569 AC: 6013 AN: 10566

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43557 AN: 67944

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.531 Hom.: 3091

Bravo AF: 0.443

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.34
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs2514675; hg19: chr8-105384931;