chr1-97736605-G-C

Position:

• chr1-97736605-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.321+3787C>G		intron_variant		ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.321+3787C>G		intron_variant		1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.321+3787C>G		intron_variant		1		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

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.868

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.49

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: rs4970728; hg19: chr1-98202161;