chr1-97354111-C-G

Variant names:

• chr1-97354111-C-G
• rs11165846
• NM_000110.4:c.2058+19450G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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

LOC105378867 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	NM_000110.4	MANE Select	c.2058+19450G>C		intron	N/A	NP_000101.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.2058+19450G>C		intron	N/A	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

African (AFR) AF: 0.248 AC: 10282 AN: 41512

American (AMR) AF: 0.324 AC: 4947 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2479 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1858 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2413 AN: 10578

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15918 AN: 67980

Other (OTH) AF: 0.251 AC: 529 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.057
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: rs11165846; hg19: chr1-97819667;