1-97221459-C-T

Variant names:

• chr1-97221459-C-T
• rs1413239
• NM_000110.4:c.2442+13393G>A

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+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
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	NM_000110.4	MANE Select	c.2442+13393G>A		intron	N/A	NP_000101.2	Q12882-1
	DPYD-AS1	NR_046590.1		n.65-43955C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.2442+13393G>A		intron	N/A	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.2610+13393G>A		intron	N/A	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.2442+13393G>A		intron	N/A	ENSP00000639974.1

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

African (AFR) AF: 0.542 AC: 22249 AN: 41046

American (AMR) AF: 0.428 AC: 6387 AN: 14940

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1139 AN: 3444

East Asian (EAS) AF: 0.580 AC: 2776 AN: 4788

South Asian (SAS) AF: 0.316 AC: 1411 AN: 4464

European-Finnish (FIN) AF: 0.355 AC: 3641 AN: 10266

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 21804 AN: 66842

Other (OTH) AF: 0.403 AC: 834 AN: 2070

Alfa AF: 0.348 Hom.: 7451

Bravo AF: 0.416

Asia WGS AF: 0.402 AC: 1394 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.18
PhyloP100		-0.043
Mutation Taster		=98/2	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: rs1413239; hg19: chr1-97687015;