NM_000110.4:c.321+3787C>G

Variant names:

• chr1-97736605-G-C
• rs4970728
• NM_000110.4:c.321+3787C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.321+3787C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,188 control chromosomes in the GnomAD database, including 55,320 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 0.85 (55320 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 5 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 Gene-Disease associations (from GenCC):

• dihydropyrimidine dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	NM_000110.4	MANE Select	c.321+3787C>G		intron	N/A	NP_000101.2
	DPYD	NM_001160301.1		c.321+3787C>G		intron	N/A	NP_001153773.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.321+3787C>G		intron	N/A	ENSP00000359211.3
	DPYD	ENST00000306031.5	TSL:1	c.321+3787C>G		intron	N/A	ENSP00000307107.5

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129339 AN: 152070 Hom.: 55295 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.850 AC: 129415 AN: 152188 Hom.: 55320 Cov.: 31 AF XY: 0.850 AC XY: 63219 AN XY: 74400

African (AFR) AF: 0.761 AC: 31579 AN: 41504

American (AMR) AF: 0.904 AC: 13831 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5104 AN: 5182

South Asian (SAS) AF: 0.911 AC: 4395 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8580 AN: 10574

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59900 AN: 68014

Other (OTH) AF: 0.868 AC: 1834 AN: 2114

Alfa AF: 0.824 Hom.: 2575

Bravo AF: 0.854

Asia WGS AF: 0.925 AC: 3214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.49
PhyloP100		0.10
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: rs4970728; hg19: chr1-98202161;