1-97354111-C-G

Position:

• chr1-97354111-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.2058+19450G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,128 control chromosomes in the GnomAD database, including 5,390 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 0.26 (5390 hom., cov: 33)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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]

LOC105378867 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2058+19450G>C		intron_variant		ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.2058+19450G>C		intron_variant		1	NM_000110.4	ENSP00000359211.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39520 AN: 152010 Hom.: 5379 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.260 AC: 39568 AN: 152128 Hom.: 5390 Cov.: 33 AF XY: 0.265 AC XY: 19690 AN XY: 74354

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.251

Alfa AF: 0.225 Hom.: 2322

Bravo AF: 0.268

Asia WGS AF: 0.414 AC: 1437 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs11165846; hg19: chr1-97819667;