rs1760217

Positions:

• chr1-97137438-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.2623-38806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,202 control chromosomes in the GnomAD database, including 2,916 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 0.19 (2916 hom., cov: 33)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYD	NM_000110.4	c.2623-38806T>C		intron_variant		ENST00000370192.8
DPYD-AS1	NR_046590.1	n.64+41452A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYD	ENST00000370192.8	c.2623-38806T>C		intron_variant		1	NM_000110.4	P1
DPYD-AS1	ENST00000422980.1	n.64+41452A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29457 AN: 152084 Hom.: 2909 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.194 AC: 29479 AN: 152202 Hom.: 2916 Cov.: 33 AF XY: 0.192 AC XY: 14285 AN XY: 74416

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.201

Alfa AF: 0.201 Hom.: 4095

Bravo AF: 0.201

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.78

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: rs1760217; hg19: chr1-97602994;