1-97798054-C-T

Variant names:

• chr1-97798054-C-T
• rs1931063
• NM_000110.4:c.233+30060G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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:40196): (DPYD antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.233+30060G>A		intron_variant	Intron 3 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.233+30060G>A		intron_variant	Intron 3 of 22	1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.233+30060G>A		intron_variant	Intron 3 of 5	1		ENSP00000307107.5
DPYD-AS2	ENST00000422259.1	n.776C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
DPYD-AS2	ENST00000431362.1	n.*186C>T		downstream_gene_variant		2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.621 AC: 25721 AN: 41426

American (AMR) AF: 0.814 AC: 12390 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2932 AN: 3468

East Asian (EAS) AF: 0.982 AC: 5067 AN: 5160

South Asian (SAS) AF: 0.817 AC: 3939 AN: 4824

European-Finnish (FIN) AF: 0.720 AC: 7610 AN: 10572

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51816 AN: 67896

Other (OTH) AF: 0.751 AC: 1586 AN: 2112

Alfa AF: 0.673 Hom.: 2174

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
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1931063; hg19: chr1-98263610;