rs11587873

Positions:

• chr1-97187514-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.2622+5555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,042 control chromosomes in the GnomAD database, including 2,666 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 0.17 (2666 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2622+5555G>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.2622+5555G>A		intron_variant		1	NM_000110.4	ENSP00000359211.3
DPYD-AS1	ENST00000422980.1	n.65-77900C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25915 AN: 151922 Hom.: 2669 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.170 AC: 25915 AN: 152042 Hom.: 2666 Cov.: 32 AF XY: 0.173 AC XY: 12844 AN XY: 74310

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.195

Alfa AF: 0.217 Hom.: 5108

Bravo AF: 0.158

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.33

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: rs11587873; hg19: chr1-97653070;