1-97798054-C-T

Position:

• chr1-97798054-C-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+30060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,890 control chromosomes in the GnomAD database, including 41,701 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 (41701 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

DPYD-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.233+30060G>A		intron_variant		ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.233+30060G>A		intron_variant		1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.233+30060G>A		intron_variant		1		ENSP00000307107.5
DPYD-AS2	ENST00000422259.1	n.776C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111812 AN: 151772 Hom.: 41682 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.748

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.737 AC: 111869 AN: 151890 Hom.: 41701 Cov.: 31 AF XY: 0.740 AC XY: 54920 AN XY: 74232

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.751

Alfa AF: 0.676 Hom.: 2003

Bravo AF: 0.739

Asia WGS AF: 0.877 AC: 3047 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.85
DANN	Benign	0.77

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: rs1931063; hg19: chr1-98263610;