rs1042482

Variant names:

• chr1-97078403-C-T
• rs1042482
• NM_000110.4:c.*573G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000110.4(DPYD):​c.*573G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 169,874 control chromosomes in the GnomAD database, including 453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (400 hom., cov: 32)
  • Exomes 𝑓: 0.072 (53 hom.)
• Consequence: DPYD NM_000110.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.265
• Publications: 8 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 Gene-Disease associations (from GenCC):

• dihydropyrimidine dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ENSG00000296260 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-97078403-C-T is Benign according to our data. Variant chr1-97078403-C-T is described in ClinVar as Benign. ClinVar VariationId is 100067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 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.*573G>A		3_prime_UTR	Exon 23 of 23	NP_000101.2	Q12882-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.*573G>A		3_prime_UTR	Exon 23 of 23	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.*573G>A		3_prime_UTR	Exon 24 of 24	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.*573G>A		3_prime_UTR	Exon 24 of 24	ENSP00000639974.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9507 AN: 152120 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0716 AC: 1262 AN: 17636 Hom.: 53 Cov.: 0 AF XY: 0.0766 AC XY: 718 AN XY: 9378

African (AFR) AF: 0.00 AC: 0 AN: 92

American (AMR) AF: 0.0428 AC: 108 AN: 2526

Ashkenazi Jewish (ASJ) AF: 0.0385 AC: 8 AN: 208

East Asian (EAS) AF: 0.108 AC: 95 AN: 882

South Asian (SAS) AF: 0.147 AC: 332 AN: 2258

European-Finnish (FIN) AF: 0.0673 AC: 33 AN: 490

Middle Eastern (MID) AF: 0.0263 AC: 1 AN: 38

European-Non Finnish (NFE) AF: 0.0618 AC: 644 AN: 10424

Other (OTH) AF: 0.0571 AC: 41 AN: 718

GnomAD4 genome AF: 0.0625 AC: 9512 AN: 152238 Hom.: 400 Cov.: 32 AF XY: 0.0639 AC XY: 4757 AN XY: 74430

African (AFR) AF: 0.0146 AC: 606 AN: 41568

American (AMR) AF: 0.0453 AC: 692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3468

East Asian (EAS) AF: 0.129 AC: 671 AN: 5188

South Asian (SAS) AF: 0.177 AC: 855 AN: 4826

European-Finnish (FIN) AF: 0.0888 AC: 941 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0790 AC: 5373 AN: 67994

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0722 Hom.: 1141

Bravo AF: 0.0564

Asia WGS AF: 0.189 AC: 656 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dihydropyrimidine dehydrogenase deficiency (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		0.27
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: rs1042482; hg19: chr1-97543959;