1-97221459-C-T

Position:

• chr1-97221459-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.2442+13393G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 149,058 control chromosomes in the GnomAD database, including 12,858 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 0.41 (12858 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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-AS1 (HGNC:40195): (DPYD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2442+13393G>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.2442+13393G>A		intron_variant		1	NM_000110.4	ENSP00000359211.3
DPYD-AS1	ENST00000422980.1	n.65-43955C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 60564 AN: 148948 Hom.: 12837 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.407 AC: 60637 AN: 149058 Hom.: 12858 Cov.: 31 AF XY: 0.408 AC XY: 29689 AN XY: 72720

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.403

Alfa AF: 0.347 Hom.: 6100

Bravo AF: 0.416

Asia WGS AF: 0.402 AC: 1394 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.18

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: rs1413239; hg19: chr1-97687015;