rs1333717

chr1-97799022-G-Achr1-97799022-G-Cchr1-97799022-G-T

Variant summary

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

The NM_000110.4(DPYD):c.233+29092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,772 control chromosomes in the GnomAD database, including 41,977 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 0.74 (41977 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYD	NM_000110.4	c.233+29092C>T		intron_variant		ENST00000370192.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYD	ENST00000370192.8	c.233+29092C>T		intron_variant		1	NM_000110.4	P1
DPYD	ENST00000306031.5	c.233+29092C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111939 AN: 151654 Hom.: 41962 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.738 AC: 111991 AN: 151772 Hom.: 41977 Cov.: 31 AF XY: 0.741 AC XY: 55001 AN XY: 74202

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.757

Alfa AF: 0.774 Hom.: 39951

Bravo AF: 0.740

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.0
Dann	Benign	0.51

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: rs1333717; hg19: chr1-98264578; COSMIC: COSV60083928; COSMIC: COSV60083928;