1-97921165-C-T

Position:

• chr1-97921165-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000646851.1(DPYD):​n.688+20408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 209,542 control chromosomes in the GnomAD database, including 1,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (919 hom., cov: 31)
  • Exomes 𝑓: 0.085 (261 hom.)
• Consequence: DPYD ENST00000646851.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-97921165-C-T is Benign according to our data. Variant chr1-97921165-C-T is described in ClinVar as [Benign]. Clinvar id is 1266319.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000646851.1	n.688+20408G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15562 AN: 151438 Hom.: 919 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00845

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0849 AC: 4925 AN: 57994 Hom.: 261 AF XY: 0.0842 AC XY: 2759 AN XY: 32770

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0750

Gnomad4 EAS exome AF: 0.00583

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0842

Gnomad4 NFE exome AF: 0.0861

Gnomad4 OTH exome AF: 0.0866

GnomAD4 genome AF: 0.103 AC: 15579 AN: 151548 Hom.: 919 Cov.: 31 AF XY: 0.104 AC XY: 7734 AN XY: 74034

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.00847

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0522 Hom.: 58

Bravo AF: 0.106

Asia WGS AF: 0.0650 AC: 228 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72981743; hg19: chr1-98386721;