chr1-97078518-A-G

Variant names:

• chr1-97078518-A-G
• rs1648944201
• NM_000110.4:c.*458T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000110.4(DPYD):​c.*458T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 34,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: DPYD NM_000110.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

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.*458T>C		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.*458T>C		3_prime_UTR	Exon 23 of 23	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.*458T>C		3_prime_UTR	Exon 24 of 24	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.*458T>C		3_prime_UTR	Exon 24 of 24	ENSP00000639974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000583 AC: 2 AN: 34330 Hom.: 0 Cov.: 0 AF XY: 0.0000549 AC XY: 1 AN XY: 18226

African (AFR) AF: 0.00 AC: 0 AN: 442

American (AMR) AF: 0.00 AC: 0 AN: 3172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 664

East Asian (EAS) AF: 0.00101 AC: 2 AN: 1972

South Asian (SAS) AF: 0.00 AC: 0 AN: 4954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20152

Other (OTH) AF: 0.00 AC: 0 AN: 1642

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		1.6

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: rs1648944201; hg19: chr1-97544074;