rs10493896

chr1-97813535-T-C

Variant summary

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

The NM_000110.4(DPYD):c.233+14579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,096 control chromosomes in the GnomAD database, including 2,411 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 0.16 (2411 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

Genes affected

DPYD (HGNC:3012): (dihydropyrimidine dehydrogenase) The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYD	NM_000110.4	c.233+14579A>G		intron_variant		ENST00000370192.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYD	ENST00000370192.8	c.233+14579A>G		intron_variant		1	NM_000110.4	P1
DPYD	ENST00000306031.5	c.233+14579A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24982 AN: 151978 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.164 AC: 24976 AN: 152096 Hom.: 2411 Cov.: 32 AF XY: 0.164 AC XY: 12168 AN XY: 74342

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.165

Alfa AF: 0.201 Hom.: 2808

Bravo AF: 0.151

Asia WGS AF: 0.0940 AC: 326 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.10
Dann	Benign	0.63

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: rs10493896; hg19: chr1-98279091;