rs56293913
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000110.4(DPYD):c.1129-15T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,456 control chromosomes in the GnomAD database, including 9,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.096 ( 849 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8536 hom. )
Consequence
DPYD
NM_000110.4 splice_polypyrimidine_tract, intron
NM_000110.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.39
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 1-97573985-A-G is Benign according to our data. Variant chr1-97573985-A-G is described in ClinVar as [Benign]. Clinvar id is 100103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-97573985-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPYD | NM_000110.4 | c.1129-15T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000370192.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPYD | ENST00000370192.8 | c.1129-15T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000110.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0957 AC: 14560AN: 152086Hom.: 849 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
14560
AN:
152086
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0956 AC: 23775AN: 248638Hom.: 1419 AF XY: 0.0987 AC XY: 13273AN XY: 134420
GnomAD3 exomes
AF:
AC:
23775
AN:
248638
Hom.:
AF XY:
AC XY:
13273
AN XY:
134420
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.103 AC: 150070AN: 1460252Hom.: 8536 Cov.: 32 AF XY: 0.103 AC XY: 75163AN XY: 726364
GnomAD4 exome
AF:
AC:
150070
AN:
1460252
Hom.:
Cov.:
32
AF XY:
AC XY:
75163
AN XY:
726364
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0957 AC: 14566AN: 152204Hom.: 849 Cov.: 32 AF XY: 0.0971 AC XY: 7226AN XY: 74408
GnomAD4 genome
?
AF:
AC:
14566
AN:
152204
Hom.:
Cov.:
32
AF XY:
AC XY:
7226
AN XY:
74408
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
149
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dihydropyrimidine dehydrogenase deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Other:1
not provided, no classification provided | literature only | Diasio Lab, Mayo Clinic | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at