rs1333727

Variant names:

• chr1-97215786-T-C
• rs1333727
• NM_000110.4:c.2442+19066A>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.2442+19066A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,902 control chromosomes in the GnomAD database, including 12,832 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 0.40 (12832 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 6 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-AS1 (HGNC:40195): (DPYD antisense RNA 1)

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 = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2442+19066A>G		intron_variant	Intron 19 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.2442+19066A>G		intron_variant	Intron 19 of 22	1	NM_000110.4	ENSP00000359211.3
DPYD-AS1	ENST00000422980.1	n.65-49628T>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60544 AN: 151784 Hom.: 12808 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.399 AC: 60620 AN: 151902 Hom.: 12832 Cov.: 32 AF XY: 0.400 AC XY: 29666 AN XY: 74226

African (AFR) AF: 0.536 AC: 22184 AN: 41412

American (AMR) AF: 0.419 AC: 6400 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2769 AN: 5122

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4818

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10550

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21850 AN: 67948

Other (OTH) AF: 0.395 AC: 833 AN: 2108

Alfa AF: 0.353 Hom.: 26655

Bravo AF: 0.416

Asia WGS AF: 0.401 AC: 1392 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	4.1
DANN	Benign	0.26
PhyloP100		-0.22
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: rs1333727; hg19: chr1-97681342;