1-97788182-A-G

Variant names:

• chr1-97788182-A-G
• rs10747486
• NM_000110.4:c.233+39932T>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.233+39932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,036 control chromosomes in the GnomAD database, including 42,727 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 0.75 (42727 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.233+39932T>C		intron_variant	Intron 3 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.233+39932T>C		intron_variant	Intron 3 of 22	1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.233+39932T>C		intron_variant	Intron 3 of 5	1		ENSP00000307107.5

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113243 AN: 151918 Hom.: 42709 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.745 AC: 113300 AN: 152036 Hom.: 42727 Cov.: 31 AF XY: 0.748 AC XY: 55579 AN XY: 74308

African (AFR) AF: 0.628 AC: 26023 AN: 41454

American (AMR) AF: 0.825 AC: 12610 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5065 AN: 5158

South Asian (SAS) AF: 0.819 AC: 3931 AN: 4800

European-Finnish (FIN) AF: 0.721 AC: 7618 AN: 10572

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52542 AN: 67978

Other (OTH) AF: 0.761 AC: 1605 AN: 2108

Alfa AF: 0.771 Hom.: 143538

Bravo AF: 0.748

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		0.071
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: rs10747486; hg19: chr1-98253738;